Plants have developed many signals and specific genes' regulations at both transcriptional and post-transcriptional levels in order to tolerate and adapt to various environmental stresses. RNA-binding proteins (RBPs...Plants have developed many signals and specific genes' regulations at both transcriptional and post-transcriptional levels in order to tolerate and adapt to various environmental stresses. RNA-binding proteins (RBPs) play crucial roles in the post- transcriptional regulation via mRNA splicing, polyadenylation, sequence editing, transport, mRNA stability, mRNA localization, and translation. In this paper, four cDNAs of glycine-rich RNA-binding proteins (GR-RBPs), named NtRGP-la, -lb, -2, and -3, were isolated from Nicotiana tabacum by RT-PCR analysis, and special emphases were given to the sequences alignment, phylogenetic analysis and gene expression. Sequences alignment revealed minor difference of cDNA sequences, but no difference of deduced proteins between N. sylvestris and N. tabacum. Phylogenetic alignment revealed that four cDNAs in tobacco were clustered into two different groups. NtRGP-2 and -3 were evolutionarily closest to Arabidopsis GR-RBPs genes and related to animal GR-RBPs genes, while NtRGP-la and -lb were closest to Gramineae GR-RBPs genes. The expression analyses of these four NtRGPs in response to different abiotic stresses revealed the similar expression pattern. Moreover, the four NtRGPs, especially NtRGP-la and NtRGP-3, were strongly induced by stresses including water, wound, cold, and high temperature, weakly induced by PEG, drought and SA, while reduced by NaC1 and unaffected by ABA treatment. The fact that all of these abiotic stresses included in our experiments affected the water balance and resulted in osmotic stress on cellular level, suggests that NtRGPs in tobacco should be a family of crucial osmosis-related proteins, and may play a key role in signal transduction with ABA-independent pathway under abiotic stresses.展开更多
Taking advantage of the fast-growing knowledge of RNA-binding proteins(RBPs)we review the signature of downregulated genes for RBPs in the transcriptome of induced pluripotent stem cell neurons(iNeurons)modelling the ...Taking advantage of the fast-growing knowledge of RNA-binding proteins(RBPs)we review the signature of downregulated genes for RBPs in the transcriptome of induced pluripotent stem cell neurons(iNeurons)modelling the neurodevelopmental Rubinstein Taybi Syndrome(RSTS)caused by mutations in the genes encoding CBP/p300 acetyltransferases.We discuss top and functionally connected downregulated genes sorted to“RNA processing”and“Ribonucleoprotein complex biogenesis”Gene Ontology clusters.The first set of downregulated RBPs includes members of hnRNHP(A1,A2B1,D,G,H2-H1,MAGOHB,PAPBC),core subunits of U small nuclear ribonucleoproteins and Serine-Arginine splicing regulators families,acting in precursor messenger RNA alternative splicing and processing.Consistent with literature findings on reduced transcript levels of serine/arginine repetitive matrix 4(SRRM4)protein,the main regulator of the neural-specific microexons splicing program upon depletion of Ep300 and Crebbp in mouse neurons,RSTS iNeurons show downregulated genes for proteins impacting this network.We link downregulated genes to neurological disorders including the new HNRNPH1-related intellectual disability syndrome with clinical overlap to RSTS.The set of downregulated genes for Ribosome biogenesis includes several components of ribosomal subunits and nucleolar proteins,such NOP58 and fibrillarin that form complexes with snoRNAs with a central role in guiding post-transcriptional modifications needed for rRNA maturation.These nucleolar proteins are“dual”players as fibrillarin is also required for epigenetic regulation of ribosomal genes and conversely NOP58-associated snoRNA levels are under the control of NOP58 interactor BMAL1,a transcriptional regulator of the circadian rhythm.Additional downregulated genes for“dual specificity”RBPs such as RUVBL1 and METTL1 highlight the links between chromatin and the RBP-ome and the contribution of perturbations in their cross-talk to RSTS.We underline the hub position of CBP/p300 in chromatin regulation,the impact of its defect on neurons’post-transcriptional regulation of gene expression and the potential use of epidrugs in therapeutics of RBP-caused neurodevelopmental disorders.展开更多
RNA-binding proteins(RBPs) are key regulators of gene expression. There are several distinct families of RBPs and they are involved in the cellular response to environmental changes, cell differentiation and cell deat...RNA-binding proteins(RBPs) are key regulators of gene expression. There are several distinct families of RBPs and they are involved in the cellular response to environmental changes, cell differentiation and cell death. The RBPs can differentially combine with RNA molecules and form ribonucleoprotein(RNP) complexes, defining the function and fate of RNA molecules in the cell. RBPs display diverse domains that allow them to be categorized into distinct families. They play important roles in the cellular response to physiological stress, in cell differentiation, and, it is believed, in the cellular localization of certain mRNAs. In several protozoa, a physiological stress(nutritional, temperature or pH) triggers differentiation to a distinct developmental stage. Most of the RBPs characterized in protozoa arise from trypanosomatids. In these protozoa gene expression regulation is mostly post-transcriptional, which suggests that some RBPs might display regulatory functions distinct from those described for other eukaryotes. mRNA stability can be altered as a response to stress. Transcripts are sequestered to RNA granules that ultimately modulate their availability to the translation machinery, storage or degradation, depending on the associated proteins. These aggregates of mRNPs containing mRNAs that are not being translated colocalize in cytoplasmic foci, and their numbers and size vary according to cell conditions such as oxidative stress, nutritional status and treatment with drugs that inhibit translation.展开更多
RNA-binding proteins(RBPs)accompany RNA from synthesis to decay,mediating every aspect of RNA metabolism and impacting diverse cellular and developmental processes in eukaryotes.Many RBPs undergo phase separation alon...RNA-binding proteins(RBPs)accompany RNA from synthesis to decay,mediating every aspect of RNA metabolism and impacting diverse cellular and developmental processes in eukaryotes.Many RBPs undergo phase separation along with their bound RNA to form and function in dynamic membraneless biomolecular condensates for spatiotemporal coordination or regulation of RNA metabolism.Increasing evidence suggests that phase-separating RBPs with RNA-binding domains and intrinsically disordered regions play important roles in plant development and stress adaptation.Here,we summarize the current knowledge about how dynamic partitioning of RBPs into condensates controls plant development and enables sensing of experimental changes to confer growth plasticity under stress conditions,with a focus on the dynamics and functional mechanisms of RBP-rich nuclear condensates and cytoplasmic granules in mediating RNA metabolism.We also discuss roles of multiple factors,such as environmental signals,protein modifications,and N6-methyladenosine RNA methylation,in modulating the phase separation behaviors of RBPs,and highlight the prospects and challenges for future research on phase-separating RBPs in crops.展开更多
The specification of germ cells in zebrafish mostly relies on an inherited mechanism by which localized maternal determinants,called germ plasm,confer germline fate in the early embryo.Extensive studies have partially...The specification of germ cells in zebrafish mostly relies on an inherited mechanism by which localized maternal determinants,called germ plasm,confer germline fate in the early embryo.Extensive studies have partially allowed the identification of key regulators governing germ plasm formation and subsequent germ cell development.RNA-binding proteins,acting in concert with other germ plasm components,play essential roles in the organization of the germ plasm and the specification,migration,maintenance,and differentiation of primordial germ cells.The loss of their functions impairs germ cell formation and causes sterility or sexual conversion.Evidence is emerging that they instruct germline development through differential regulation of mRNA fates in somatic and germ cells.However,the challenge remains to decipher the complex interplay of maternal germ plasm components in germ plasm compartmentalization and germ cell specification.Because failure to control the developmental outcome of germ cells disrupts the formation of gametes,it is important to gain a complete picture of regulatory mechanisms operating in the germ cell lineage.This review sheds light on the contributions of RNA-binding proteins to germ cell development in zebrafish and highlights intriguing questions that remain open for future investigation.展开更多
BACKGROUND Recently,type 2 diabetic osteoporosis(T2DOP)has become a research hotspot for the complications of diabetes,but the specific mechanism of its occurrence and development remains unknown.Ferroptosis caused by...BACKGROUND Recently,type 2 diabetic osteoporosis(T2DOP)has become a research hotspot for the complications of diabetes,but the specific mechanism of its occurrence and development remains unknown.Ferroptosis caused by iron overload is con-sidered an important cause of T2DOP.Polycytosine RNA-binding protein 1(PCBP1),an iron ion chaperone,is considered a protector of ferroptosis.AIM To investigate the existence of ferroptosis and specific role of PCBP1 in the development of type 2 diabetes.METHODS A cell counting kit-8 assay was used to detect changes in osteoblast viability under high glucose(HG)and/or ferroptosis inhibitors at different concentrations and times.Transmission electron microscopy was used to examine the morpho-logical changes in the mitochondria of osteoblasts under HG,and western blotting was used to detect the expression levels of PCBP1,ferritin,and the ferroptosis-related protein glutathione peroxidase 4(GPX4).A lentivirus silenced and overex-pressed PCBP1.Western blotting was used to detect the expression levels of the osteoblast functional proteins osteoprotegerin(OPG)and osteocalcin(OCN),whereas flow cytometry was used to detect changes in reactive oxygen species(ROS)levels in each group.RESULTS Under HG,the viability of osteoblasts was considerably decreased,the number of mitochondria undergoing atrophy was considerably increased,PCBP1 and ferritin expression levels were increased,and GPX4 expression was decreased.Western blotting results demonstrated that infection with lentivirus overexpressing PCBP1,increased the expression levels of ferritin,GPX4,OPG,and OCN,compared with the HG group.Flow cytometry results showed a reduction in ROS,and an opposite result was obtained after silencing PCBP1.CONCLUSION PCBP1 may protect osteoblasts and reduce the harm caused by ferroptosis by promoting ferritin expression under a HG environment.Moreover,PCBP1 may be a potential therapeutic target for T2DOP.展开更多
Emerging studies support that RNA-binding proteins (RBPs) play critical roles in human biology and pathogenesis. RBPs are essential players in RNA processing and metabolism, including pre-mRNA splicing, polyadenylat...Emerging studies support that RNA-binding proteins (RBPs) play critical roles in human biology and pathogenesis. RBPs are essential players in RNA processing and metabolism, including pre-mRNA splicing, polyadenylation, transport, surveillance, mRNA localization, mRNA stability control, translational control and editing of various types of RNAs. Aberrant expression of and mutations in RBP genes affect various steps of RNA processing, altering target gene function. RBPs have been associ- ated with various diseases, including neurological diseases. Here, we mainly focus on selected RNA-binding proteins including Nova-i/Nova-2, HuR/HuB/HuC/HuD, TDP-43, Fus, Rbfoxl/Rbfox2, QKI and FMRP, discussing their function and roles in human diseases.展开更多
The complex responses of eukaryotic cells to external factors are governed by several transcriptional and post-transcriptional processes. Several of them occur in the nucleus and have been linked to the action of non-...The complex responses of eukaryotic cells to external factors are governed by several transcriptional and post-transcriptional processes. Several of them occur in the nucleus and have been linked to the action of non-proteincoding RNAs (or npcRNAs), both long and small npcRNAs, that recently emerged as major regulators of gene expression. Regulatory npcRNAs acting in the nucleus include silencing-related RNAs, intergenic npcRNAs, natural antisense RNAs, and other aberrant RNAs resulting from the interplay between global transcription and RNA processing activities (such as Dicers and RNA-dependent polymerases). Generally, the resulting npcRNAs exert their regulatory effects through interactions with RNA-binding proteins (or RBPs) within ribonucleoprotein particles (or RNPs). A large group of RBPs are implicated in the silencing machinery through small interfering RNAs (siRNAs) and their localization suggests that several act in the nucleus to trigger epigenetic and chromatin changes at a whole-genome scale. Other nuclear RBPs interact with npcRNAs and change their localization. In the fission yeast, the RNA-binding Mei2p protein, playing pivotal roles in meiosis, interact with a meiotic npcRNA involved in its nuclear re-localization. Related processes have been identified in plants and the ENOD40 npcRNA was shown to re-localize a nuclear-speckle RBP from the nucleus to the cytoplasm in Medicago truncatula. Plant RBPs have been also implicated in RNA-mediated chromatin silencing in the FLC locus through interaction with specific antisense transcripts. In this review, we discuss the interactions between RBPs and npcRNAs in the context of nuclear-related processes and their implication in plant development and stress responses. We propose that these interactions may add a regulatory layer that modulates the interactions between the nuclear genome and the environment and, consequently, control plant developmental plasticity.展开更多
In this study,we investigated the effects of major royal jelly proteins(MRJPs)on the estrogen,gut microbiota,and immunological responses in mice.Mice given 250 or 500 mg/kg,not 125 mg/kg of MRJPs,enhanced the prolifer...In this study,we investigated the effects of major royal jelly proteins(MRJPs)on the estrogen,gut microbiota,and immunological responses in mice.Mice given 250 or 500 mg/kg,not 125 mg/kg of MRJPs,enhanced the proliferation of splenocytes in response to mitogens.The splenocytes and mesenteric lymphocytes activated by T-cell mitogens(Con A and anti-CD3/CD28 antibodies)released high levels of IL-2 but low levels of IFN-γand IL-17A.The release of IL-4 was unaffected by MRJPs.Additionally,splenocytes and mesenteric lymphocytes activated by LPS were prevented by MRJPs at the same dose as that required for producing IL-1βand IL-6,two pro-inflammatory cytokines.The production of IL-1β,IL-6,and IFN-γwas negatively associated with estrogen levels,which were higher in the MRJP-treated animals than in the control group.Analysis of the gut microbiota revealed that feeding mice 250 mg/kg of MRJPs maintained the stability of the natural intestinal microflora of mice.Additionally,the LEf Se analysis identified biomarkers in the MRJP-treated mice,including Prevotella,Bacillales,Enterobacteriales,Gammaproteobacteria,Candidatus_Arthromitus,and Shigella.Our results showed that MRJPs are important components of royal jelly that modulate host immunity and hormone levels and help maintain gut microbiota stability.展开更多
Objective To construct and verificate an RNA-binding protein(RBP)-associated prognostic model for gliomas using integrated bioinformatics analysis.Methods RNA-sequencing and clinic pathological data of glioma patients...Objective To construct and verificate an RNA-binding protein(RBP)-associated prognostic model for gliomas using integrated bioinformatics analysis.Methods RNA-sequencing and clinic pathological data of glioma patients from The Cancer Genome Atlas(TCGA)database and the Chinese Glioma Genome Atlas database(CGGA)were downloaded.The aberrantly expressed RBPs were investigated between gliomas and normal samples in TCGA database.We then identified prognosis related hub genes and constructed a prognostic model.This model was further validated in the CGGA-693 and CGGA-325 cohorts.Results Totally 174 differently expressed genes-encoded RBPs were identified,containing 85 down-regulated and 89 up-regulated genes.We identified five genes-encoded RBPs(ERI1,RPS2,BRCA1,NXT1,and TRIM21)as prognosis related key genes and constructed a prognostic model.Overall survival(OS)analysis revealed that the patients in the high-risk subgroup based on the model were worse than those in the low-risk subgroup.The area under the receiver operator characteristic curve(AUC)of the prognostic model was 0.836 in the TCGA dataset and 0.708 in the CGGA-693 dataset,demonstrating a favorable prognostic model.Survival analyses of the five RBPs in the CGGA-325 cohort validated the findings.A nomogram was constructed based on the five genes and validated in the TCGA cohort,confirming a promising discriminating ability for gliomas.Conclusion The prognostic model of the five RBPs might serve as an independent prognostic algorithm for gliomas.展开更多
Parkinson’s disease is a common neurodegenerative disorder that is associated with abnormal aggregation and accumulation of neurotoxic proteins,includingα-synuclein,amyloid-β,and tau,in addition to the impaired eli...Parkinson’s disease is a common neurodegenerative disorder that is associated with abnormal aggregation and accumulation of neurotoxic proteins,includingα-synuclein,amyloid-β,and tau,in addition to the impaired elimination of these neurotoxic protein.Atypical parkinsonism,which has the same clinical presentation and neuropathology as Parkinson’s disease,expands the disease landscape within the continuum of Parkinson’s disease and related disorders.The glymphatic system is a waste clearance system in the brain,which is responsible for eliminating the neurotoxic proteins from the interstitial fluid.Impairment of the glymphatic system has been proposed as a significant contributor to the development and progression of neurodegenerative disease,as it exacerbates the aggregation of neurotoxic proteins and deteriorates neuronal damage.Therefore,impairment of the glymphatic system could be considered as the final common pathway to neurodegeneration.Previous evidence has provided initial insights into the potential effect of the impaired glymphatic system on Parkinson’s disease and related disorders;however,many unanswered questions remain.This review aims to provide a comprehensive summary of the growing literature on the glymphatic system in Parkinson’s disease and related disorders.The focus of this review is on identifying the manifestations and mechanisms of interplay between the glymphatic system and neurotoxic proteins,including loss of polarization of aquaporin-4 in astrocytic endfeet,sleep and circadian rhythms,neuroinflammation,astrogliosis,and gliosis.This review further delves into the underlying pathophysiology of the glymphatic system in Parkinson’s disease and related disorders,and the potential implications of targeting the glymphatic system as a novel and promising therapeutic strategy.展开更多
Endothelial cell dysfunction is a term which implies the dysregulation of normal endothelial cell functions,including impairment of the barrier functions,control of vascular tone,disturbance of proliferative and migra...Endothelial cell dysfunction is a term which implies the dysregulation of normal endothelial cell functions,including impairment of the barrier functions,control of vascular tone,disturbance of proliferative and migratory capacity of endothelial cells,as well as control of leukocyte trafficking.Endothelial dysfunction is an early step in vascular inflammatory diseases such as atherosclerosis,diabetic vascular complications,sepsis-induced or severe virus infection-induced organ injuries.The expressions of inflammatory cytokines and vascular adhesion molecules induced by various stimuli,such as modified lipids,smoking,advanced glycation end products and bacteria toxin,significantly contribute to the development of endothelial dysfunction.The transcriptional regulation of inflammatory cytokines and vascular adhesion molecules has been well-studied.However,the regulation of those gene expressions at post-transcriptional level is emerging.RNA-binding proteins have emerged as critical regulators of gene expression acting predominantly at the post-transcriptional level in microRNA-dependent or independent manners.This review summarizes the latest insights into the roles of RNA-binding proteins in controlling vascular endothelial cell functions and their contribution to the pathogenesis of vascular inflammatory diseases.展开更多
Adult stem cells that reside in particular types of tissues are responsible for tissue homeostasis and regeneration.Cellular functions of adult stem cells are intricately related to the gene expression programs in tho...Adult stem cells that reside in particular types of tissues are responsible for tissue homeostasis and regeneration.Cellular functions of adult stem cells are intricately related to the gene expression programs in those cells.Past research has demonstrated that regulation of gene expression at the transcriptional level can decisively alter cell fate of stem cells.However,cellular contents of mRNAs are sometimes not equivalent to proteins,the functional units of cells.It is increasingly realized that post-transcriptional and translational regulation of gene expression are also fundamental for stem cell functions.Compared to differentiated somatic cells,effects on cellular status manifested by varied expression of RNA-binding proteins and global protein synthesis have been demonstrated in several stem cell systems.Through the cooperation of both cis-elements of mRNAs and trans-acting RNA-binding proteins that are intimately associated with them,regulation of localization,stability,and translational status of mRNAs directly influences the self-renewal and differentiation of stem cells.Previous studies have uncovered some of the molecular mechanisms that underlie the functions of RNA-binding proteins in stem cells in invertebrate species.However,their roles in adult stem cells in mammals are just beginning to be unveiled.This review highlights some of the RNA-binding proteins that play important functions during the maintenance and differentiation of mouse male germline stem cells,the adult stem cells in the male reproductive organ.展开更多
Essential proteins are inseparable in cell growth and survival. The study of essential proteins is important for understanding cellular functions and biological mechanisms. Therefore, various computable methods have b...Essential proteins are inseparable in cell growth and survival. The study of essential proteins is important for understanding cellular functions and biological mechanisms. Therefore, various computable methods have been proposed to identify essential proteins. Unfortunately, most methods based on network topology only consider the interactions between a protein and its neighboring proteins, and not the interactions with its higher-order distance proteins. In this paper, we propose the DSEP algorithm in which we integrated network topology properties and subcellular localization information in protein–protein interaction(PPI) networks based on four-order distances, and then used random walks to identify the essential proteins. We also propose a method to calculate the finite-order distance of the network, which can greatly reduce the time complexity of our algorithm. We conducted a comprehensive comparison of the DSEP algorithm with 11 existing classical algorithms to identify essential proteins with multiple evaluation methods. The results show that DSEP is superior to these 11 methods.展开更多
Protein-based therapeutics (PPTs) are drugs used to treat a variety of different conditions in the human body by alleviating enzymatic deficiencies, augmenting other proteins and drugs, modulating signal pathways, and...Protein-based therapeutics (PPTs) are drugs used to treat a variety of different conditions in the human body by alleviating enzymatic deficiencies, augmenting other proteins and drugs, modulating signal pathways, and more. However, many PPTs struggle from a short half-life due to degradation caused by irreversible protein aggregation in the bloodstream. Currently, the most researched strategies for improving the efficiency and longevity of PPTs are post-translational modifications (PTMs). The goal of our research was to determine which type of PTM increases longevity the most for each of three commonly-used therapeutic proteins by comparing the docking scores (DS) and binding free energies (BFE) from protein aggregation and reception simulations. DS and BFE values were used to create a quantitative index that outputs a relative number from −1 to 1 to show reduced performance, no change, or increased performance. Results showed that methylation was the most beneficial for insulin (p < 0.1) and human growth hormone (p < 0.0001), and both phosphorylation and methylation were somewhat optimal for erythropoietin (p < 0.1 and p < 0.0001, respectively). Acetylation consistently provided the worst benefits with the most negative indices, while methylation had the most positive indices throughout. However, PTM efficacy varied between PPTs, supporting previous studies regarding how each PTM can confer different benefits based on the unique structures of recipient proteins.展开更多
Hyphal fusion(anastomosis)is a common process serving many important functions at various developmental stages in the life cycle of ascomycetous fungi.However,the biological roles and molecular mechanisms in plant pat...Hyphal fusion(anastomosis)is a common process serving many important functions at various developmental stages in the life cycle of ascomycetous fungi.However,the biological roles and molecular mechanisms in plant pathogenic fungi were widely unknown.In this study,a hyphal fusion protein FpHam-2 was screened from a T-DNA insertion mutant library of Fusarium pseudograminearum,and FpHam-2 interacts with another 2 hyphal fusion protein homologues FpHam-3 and FpHam-4.Each of these 3 genes deletion mutant revealed in similar defective phenotypes compared with the WT and complemented strains,including reduction in growth rate,defects in hyphal fusion and conidiation,more sensitive for cell membrane,cell wall and oxidative stress responses,and decreased in virulence.The yeast two-hybrid assay was used to identify that FpHam-2 interacts with 3 autophagy-related proteins,including FpAtg3,FpAtg28 and FpAtg33.Furthermore,FpHam-2-deletion mutant showed decreased accumulation of autophagic bodies in hypha.In conclusion,FpHam-2,FpHam-3 and FpHam-4 have an essential role for hyphal fusion and regulating the growth,conidiation and virulence in F.pseudograminearum.展开更多
Plant calmodulins(CaMs)and calmodulin-like proteins(CMLs)mediate Ca~(2+)signaling in response to abiotic stresses.Manipulation of this signaling in crops could increase stress tolerance.We review methods for detecting...Plant calmodulins(CaMs)and calmodulin-like proteins(CMLs)mediate Ca~(2+)signaling in response to abiotic stresses.Manipulation of this signaling in crops could increase stress tolerance.We review methods for detecting Ca~(2+)signals,regulatory roles of Ca Ms and CMLs,binding targets,and Ca~(2+)networks under abiotic stress in organelles.展开更多
BACKGROUND Heat shock proteins(HSPs)are molecular chaperones that play an important role in cellular protection against stress events and have been reported to be overex-pressed in many cancers.The prognostic signific...BACKGROUND Heat shock proteins(HSPs)are molecular chaperones that play an important role in cellular protection against stress events and have been reported to be overex-pressed in many cancers.The prognostic significance of HSPs and their regulatory factors,such as heat shock factor 1(HSF1)and CHIP,are poorly understood.AIM To investigate the relationship between HSP expression and prognosis in esophageal and esophagogastric cancer.METHODS A systematic review was conducted in accordance with PRISMA recommend-ations(PROSPERO:CRD42022370653),on Embase,PubMed,Cochrane,and LILACS.Cohort,case-control,and cross-sectional studies of patients with eso-phagus or esophagogastric cancer were included.HSP-positive patients were compared with HSP-negative,and the endpoints analyzed were lymph node metastasis,tumor depth,distant metastasis,and overall survival(OS).HSPs were stratified according to the HSP family,and the summary risk difference(RD)was calculated using a random-effect model.RESULTS The final selection comprised 27 studies,including esophageal squamous cell carcinoma(21),esophagogastric adenocarcinoma(5),and mixed neoplasms(1).The pooled sample size was 3465 patients.HSP40 and 60 were associated with a higher 3-year OS[HSP40:RD=0.22;95%confidence interval(CI):0.09-0.35;HSP60:RD=0.33;95%CI:0.17-0.50],while HSF1 was associated with a poor 3-year OS(RD=-0.22;95%CI:-0.32 to-0.12).The other HSP families were not associated with long-term survival.HSF1 was associated with a higher probability of lymph node metastasis(RD=-0.16;95%CI:-0.29 to-0.04).HSP40 was associated with a lower probability of lymph node dissemination(RD=0.18;95%CI:0.03-0.33).The expression of other HSP families was not significantly related to tumor depth and lymph node or distant metastasis.CONCLUSION The expression levels of certain families of HSP,such as HSP40 and 60 and HSF1,are associated with long-term survival and lymph node dissemination in patients with esophageal and esophagogastric cancer.展开更多
Cotton provides the most abundant natural fiber for the textile industry.The mature cotton fiber largely consists of secondary cell walls with the highest proportion of cellulose and a small amount of hemicellulose an...Cotton provides the most abundant natural fiber for the textile industry.The mature cotton fiber largely consists of secondary cell walls with the highest proportion of cellulose and a small amount of hemicellulose and lignin.To dissect the roles of hemicellulosic polysaccharides during fiber development,four IRREGULAR XYLEM 15(IRX15)genes,GhIRX15-1/-2/-3/-4,were functionally characterized in cotton.These genes encode DUF579 domain-containing proteins,which are homologs of AtIRX15 involved in xylan biosynthesis.The four GhIRX15 genes were predominantly expressed during fiber secondary wall thickening,and the encoded proteins were localized to the Golgi apparatus.Each GhIRX15 gene could restore the xylan deficient phenotype in the Arabidopsis irx15irx15l double mutant.Silencing of GhIRX15s in cotton resulted in shorter mature fibers with a thinner cell wall and reduced cellulose content as compared to the wild type.Intriguingly,GhIRX15-2 and GhIRX15-4 formed homodimers and heterodimers.In addition,the GhIRX15s showed physical interaction with glycosyltransferases GhGT43C,GhGT47A and GhGT47B,which are responsible for synthesis of the xylan backbone and reducing end sequence.Moreover,the GhIRX15s can form heterocomplexes with enzymes involved in xylan modification and side chain synthesis,such as GhGUX1/2,GhGXM1/2 and GhTBL1.These findings suggest that GhIRX15s participate in fiber xylan biosynthesis and modulate fiber development via forming large multiprotein complexes.展开更多
Food allergens are mainly naturally-occurring proteins with immunoglobulin E(IgE)-binding epitopes.Understanding the structural and immunogenic characteristics of allergenic proteins is essential in assessing whether ...Food allergens are mainly naturally-occurring proteins with immunoglobulin E(IgE)-binding epitopes.Understanding the structural and immunogenic characteristics of allergenic proteins is essential in assessing whether and how food processing techniques reduce allergenicity.We here discuss the impacts of food processing technologies on the modification of physicochemical,structural,and immunogenic properties of allergenic proteins.Detection techniques for characterizing changes in these properties of food allergens are summarized.Food processing helps to reduce allergenicity by aggregating or denaturing proteins,which masks,modifies,or destroys antigenic epitopes,whereas,it cannot eliminate allergenicity completely,and sometimes even improves allergenicity by exposing new epitopes.Moreover,most food processing techniques have been tested on purified food allergens rather than food products due to potential interference of other food components.We provide guidance for further development of processing operations that can decrease the allergenicity of allergenic food proteins without negatively impacting the nutritional profile.展开更多
基金funded by the National Natural Science Foundation of China (30560062)the Natural Science Foundation of Yunnan Province, China (2003C0342M)the Science-Technology Foundation of Tobacco Company of Yunnan Province, China (06A02)
文摘Plants have developed many signals and specific genes' regulations at both transcriptional and post-transcriptional levels in order to tolerate and adapt to various environmental stresses. RNA-binding proteins (RBPs) play crucial roles in the post- transcriptional regulation via mRNA splicing, polyadenylation, sequence editing, transport, mRNA stability, mRNA localization, and translation. In this paper, four cDNAs of glycine-rich RNA-binding proteins (GR-RBPs), named NtRGP-la, -lb, -2, and -3, were isolated from Nicotiana tabacum by RT-PCR analysis, and special emphases were given to the sequences alignment, phylogenetic analysis and gene expression. Sequences alignment revealed minor difference of cDNA sequences, but no difference of deduced proteins between N. sylvestris and N. tabacum. Phylogenetic alignment revealed that four cDNAs in tobacco were clustered into two different groups. NtRGP-2 and -3 were evolutionarily closest to Arabidopsis GR-RBPs genes and related to animal GR-RBPs genes, while NtRGP-la and -lb were closest to Gramineae GR-RBPs genes. The expression analyses of these four NtRGPs in response to different abiotic stresses revealed the similar expression pattern. Moreover, the four NtRGPs, especially NtRGP-la and NtRGP-3, were strongly induced by stresses including water, wound, cold, and high temperature, weakly induced by PEG, drought and SA, while reduced by NaC1 and unaffected by ABA treatment. The fact that all of these abiotic stresses included in our experiments affected the water balance and resulted in osmotic stress on cellular level, suggests that NtRGPs in tobacco should be a family of crucial osmosis-related proteins, and may play a key role in signal transduction with ABA-independent pathway under abiotic stresses.
基金This work was supported by Italian Ministery of Health RC 08C921 to LL,Istituto Auxologico Italiano,IRCCs.
文摘Taking advantage of the fast-growing knowledge of RNA-binding proteins(RBPs)we review the signature of downregulated genes for RBPs in the transcriptome of induced pluripotent stem cell neurons(iNeurons)modelling the neurodevelopmental Rubinstein Taybi Syndrome(RSTS)caused by mutations in the genes encoding CBP/p300 acetyltransferases.We discuss top and functionally connected downregulated genes sorted to“RNA processing”and“Ribonucleoprotein complex biogenesis”Gene Ontology clusters.The first set of downregulated RBPs includes members of hnRNHP(A1,A2B1,D,G,H2-H1,MAGOHB,PAPBC),core subunits of U small nuclear ribonucleoproteins and Serine-Arginine splicing regulators families,acting in precursor messenger RNA alternative splicing and processing.Consistent with literature findings on reduced transcript levels of serine/arginine repetitive matrix 4(SRRM4)protein,the main regulator of the neural-specific microexons splicing program upon depletion of Ep300 and Crebbp in mouse neurons,RSTS iNeurons show downregulated genes for proteins impacting this network.We link downregulated genes to neurological disorders including the new HNRNPH1-related intellectual disability syndrome with clinical overlap to RSTS.The set of downregulated genes for Ribosome biogenesis includes several components of ribosomal subunits and nucleolar proteins,such NOP58 and fibrillarin that form complexes with snoRNAs with a central role in guiding post-transcriptional modifications needed for rRNA maturation.These nucleolar proteins are“dual”players as fibrillarin is also required for epigenetic regulation of ribosomal genes and conversely NOP58-associated snoRNA levels are under the control of NOP58 interactor BMAL1,a transcriptional regulator of the circadian rhythm.Additional downregulated genes for“dual specificity”RBPs such as RUVBL1 and METTL1 highlight the links between chromatin and the RBP-ome and the contribution of perturbations in their cross-talk to RSTS.We underline the hub position of CBP/p300 in chromatin regulation,the impact of its defect on neurons’post-transcriptional regulation of gene expression and the potential use of epidrugs in therapeutics of RBP-caused neurodevelopmental disorders.
文摘RNA-binding proteins(RBPs) are key regulators of gene expression. There are several distinct families of RBPs and they are involved in the cellular response to environmental changes, cell differentiation and cell death. The RBPs can differentially combine with RNA molecules and form ribonucleoprotein(RNP) complexes, defining the function and fate of RNA molecules in the cell. RBPs display diverse domains that allow them to be categorized into distinct families. They play important roles in the cellular response to physiological stress, in cell differentiation, and, it is believed, in the cellular localization of certain mRNAs. In several protozoa, a physiological stress(nutritional, temperature or pH) triggers differentiation to a distinct developmental stage. Most of the RBPs characterized in protozoa arise from trypanosomatids. In these protozoa gene expression regulation is mostly post-transcriptional, which suggests that some RBPs might display regulatory functions distinct from those described for other eukaryotes. mRNA stability can be altered as a response to stress. Transcripts are sequestered to RNA granules that ultimately modulate their availability to the translation machinery, storage or degradation, depending on the associated proteins. These aggregates of mRNPs containing mRNAs that are not being translated colocalize in cytoplasmic foci, and their numbers and size vary according to cell conditions such as oxidative stress, nutritional status and treatment with drugs that inhibit translation.
基金supported by the National Research Foundation Competitive Research Programme(NRF-CRP22-2019-0001)the intramural funding from Temasek Life Sciences Laboratory。
文摘RNA-binding proteins(RBPs)accompany RNA from synthesis to decay,mediating every aspect of RNA metabolism and impacting diverse cellular and developmental processes in eukaryotes.Many RBPs undergo phase separation along with their bound RNA to form and function in dynamic membraneless biomolecular condensates for spatiotemporal coordination or regulation of RNA metabolism.Increasing evidence suggests that phase-separating RBPs with RNA-binding domains and intrinsically disordered regions play important roles in plant development and stress adaptation.Here,we summarize the current knowledge about how dynamic partitioning of RBPs into condensates controls plant development and enables sensing of experimental changes to confer growth plasticity under stress conditions,with a focus on the dynamics and functional mechanisms of RBP-rich nuclear condensates and cytoplasmic granules in mediating RNA metabolism.We also discuss roles of multiple factors,such as environmental signals,protein modifications,and N6-methyladenosine RNA methylation,in modulating the phase separation behaviors of RBPs,and highlight the prospects and challenges for future research on phase-separating RBPs in crops.
文摘The specification of germ cells in zebrafish mostly relies on an inherited mechanism by which localized maternal determinants,called germ plasm,confer germline fate in the early embryo.Extensive studies have partially allowed the identification of key regulators governing germ plasm formation and subsequent germ cell development.RNA-binding proteins,acting in concert with other germ plasm components,play essential roles in the organization of the germ plasm and the specification,migration,maintenance,and differentiation of primordial germ cells.The loss of their functions impairs germ cell formation and causes sterility or sexual conversion.Evidence is emerging that they instruct germline development through differential regulation of mRNA fates in somatic and germ cells.However,the challenge remains to decipher the complex interplay of maternal germ plasm components in germ plasm compartmentalization and germ cell specification.Because failure to control the developmental outcome of germ cells disrupts the formation of gametes,it is important to gain a complete picture of regulatory mechanisms operating in the germ cell lineage.This review sheds light on the contributions of RNA-binding proteins to germ cell development in zebrafish and highlights intriguing questions that remain open for future investigation.
基金Supported by the National Natural Science Foundation of China,No.81471094 and No.82202743.
文摘BACKGROUND Recently,type 2 diabetic osteoporosis(T2DOP)has become a research hotspot for the complications of diabetes,but the specific mechanism of its occurrence and development remains unknown.Ferroptosis caused by iron overload is con-sidered an important cause of T2DOP.Polycytosine RNA-binding protein 1(PCBP1),an iron ion chaperone,is considered a protector of ferroptosis.AIM To investigate the existence of ferroptosis and specific role of PCBP1 in the development of type 2 diabetes.METHODS A cell counting kit-8 assay was used to detect changes in osteoblast viability under high glucose(HG)and/or ferroptosis inhibitors at different concentrations and times.Transmission electron microscopy was used to examine the morpho-logical changes in the mitochondria of osteoblasts under HG,and western blotting was used to detect the expression levels of PCBP1,ferritin,and the ferroptosis-related protein glutathione peroxidase 4(GPX4).A lentivirus silenced and overex-pressed PCBP1.Western blotting was used to detect the expression levels of the osteoblast functional proteins osteoprotegerin(OPG)and osteocalcin(OCN),whereas flow cytometry was used to detect changes in reactive oxygen species(ROS)levels in each group.RESULTS Under HG,the viability of osteoblasts was considerably decreased,the number of mitochondria undergoing atrophy was considerably increased,PCBP1 and ferritin expression levels were increased,and GPX4 expression was decreased.Western blotting results demonstrated that infection with lentivirus overexpressing PCBP1,increased the expression levels of ferritin,GPX4,OPG,and OCN,compared with the HG group.Flow cytometry results showed a reduction in ROS,and an opposite result was obtained after silencing PCBP1.CONCLUSION PCBP1 may protect osteoblasts and reduce the harm caused by ferroptosis by promoting ferritin expression under a HG environment.Moreover,PCBP1 may be a potential therapeutic target for T2DOP.
基金Zhou HuaLin is supported by National Basic Research Program of China(2013CB917803)research fund for the State Key Laboratory of Cog-nitive Neuroscience and Learning from Institute of Biophysics,Chinese Academy of Sciences(7Y1SNY7007)+3 种基金supported by the Ross Maclean Senior Research Fellowship and the Peter Goodenough BequestZhu Li and Liu JiangHong are supported by grants from the Na-tional Major Basic Research Program of China(2010CB529603)the National Natural Science Foundation of China(91132710,31200561)Jane Y.Wu is supported by the US National Institutes of Health
文摘Emerging studies support that RNA-binding proteins (RBPs) play critical roles in human biology and pathogenesis. RBPs are essential players in RNA processing and metabolism, including pre-mRNA splicing, polyadenylation, transport, surveillance, mRNA localization, mRNA stability control, translational control and editing of various types of RNAs. Aberrant expression of and mutations in RBP genes affect various steps of RNA processing, altering target gene function. RBPs have been associ- ated with various diseases, including neurological diseases. Here, we mainly focus on selected RNA-binding proteins including Nova-i/Nova-2, HuR/HuB/HuC/HuD, TDP-43, Fus, Rbfoxl/Rbfox2, QKI and FMRP, discussing their function and roles in human diseases.
文摘The complex responses of eukaryotic cells to external factors are governed by several transcriptional and post-transcriptional processes. Several of them occur in the nucleus and have been linked to the action of non-proteincoding RNAs (or npcRNAs), both long and small npcRNAs, that recently emerged as major regulators of gene expression. Regulatory npcRNAs acting in the nucleus include silencing-related RNAs, intergenic npcRNAs, natural antisense RNAs, and other aberrant RNAs resulting from the interplay between global transcription and RNA processing activities (such as Dicers and RNA-dependent polymerases). Generally, the resulting npcRNAs exert their regulatory effects through interactions with RNA-binding proteins (or RBPs) within ribonucleoprotein particles (or RNPs). A large group of RBPs are implicated in the silencing machinery through small interfering RNAs (siRNAs) and their localization suggests that several act in the nucleus to trigger epigenetic and chromatin changes at a whole-genome scale. Other nuclear RBPs interact with npcRNAs and change their localization. In the fission yeast, the RNA-binding Mei2p protein, playing pivotal roles in meiosis, interact with a meiotic npcRNA involved in its nuclear re-localization. Related processes have been identified in plants and the ENOD40 npcRNA was shown to re-localize a nuclear-speckle RBP from the nucleus to the cytoplasm in Medicago truncatula. Plant RBPs have been also implicated in RNA-mediated chromatin silencing in the FLC locus through interaction with specific antisense transcripts. In this review, we discuss the interactions between RBPs and npcRNAs in the context of nuclear-related processes and their implication in plant development and stress responses. We propose that these interactions may add a regulatory layer that modulates the interactions between the nuclear genome and the environment and, consequently, control plant developmental plasticity.
基金financially supported by the National Natural Science Foundation of China(U2004104)the Natural Science Foundation of Henan Province(202300410080)+2 种基金the Key Project of Henan Education Committee(21A310005)the Internal Fund of Hebei University of Economics and Business(2020ZD10)the Postgraduate“Talent Program”of Henan University(SYL20060187 and SYL20060189)。
文摘In this study,we investigated the effects of major royal jelly proteins(MRJPs)on the estrogen,gut microbiota,and immunological responses in mice.Mice given 250 or 500 mg/kg,not 125 mg/kg of MRJPs,enhanced the proliferation of splenocytes in response to mitogens.The splenocytes and mesenteric lymphocytes activated by T-cell mitogens(Con A and anti-CD3/CD28 antibodies)released high levels of IL-2 but low levels of IFN-γand IL-17A.The release of IL-4 was unaffected by MRJPs.Additionally,splenocytes and mesenteric lymphocytes activated by LPS were prevented by MRJPs at the same dose as that required for producing IL-1βand IL-6,two pro-inflammatory cytokines.The production of IL-1β,IL-6,and IFN-γwas negatively associated with estrogen levels,which were higher in the MRJP-treated animals than in the control group.Analysis of the gut microbiota revealed that feeding mice 250 mg/kg of MRJPs maintained the stability of the natural intestinal microflora of mice.Additionally,the LEf Se analysis identified biomarkers in the MRJP-treated mice,including Prevotella,Bacillales,Enterobacteriales,Gammaproteobacteria,Candidatus_Arthromitus,and Shigella.Our results showed that MRJPs are important components of royal jelly that modulate host immunity and hormone levels and help maintain gut microbiota stability.
基金supported by the National Natural Science Foundation of China(No.82072795).
文摘Objective To construct and verificate an RNA-binding protein(RBP)-associated prognostic model for gliomas using integrated bioinformatics analysis.Methods RNA-sequencing and clinic pathological data of glioma patients from The Cancer Genome Atlas(TCGA)database and the Chinese Glioma Genome Atlas database(CGGA)were downloaded.The aberrantly expressed RBPs were investigated between gliomas and normal samples in TCGA database.We then identified prognosis related hub genes and constructed a prognostic model.This model was further validated in the CGGA-693 and CGGA-325 cohorts.Results Totally 174 differently expressed genes-encoded RBPs were identified,containing 85 down-regulated and 89 up-regulated genes.We identified five genes-encoded RBPs(ERI1,RPS2,BRCA1,NXT1,and TRIM21)as prognosis related key genes and constructed a prognostic model.Overall survival(OS)analysis revealed that the patients in the high-risk subgroup based on the model were worse than those in the low-risk subgroup.The area under the receiver operator characteristic curve(AUC)of the prognostic model was 0.836 in the TCGA dataset and 0.708 in the CGGA-693 dataset,demonstrating a favorable prognostic model.Survival analyses of the five RBPs in the CGGA-325 cohort validated the findings.A nomogram was constructed based on the five genes and validated in the TCGA cohort,confirming a promising discriminating ability for gliomas.Conclusion The prognostic model of the five RBPs might serve as an independent prognostic algorithm for gliomas.
基金supported by the National Key R&D Program of China,No.2021YFF0702203(to HYL)the National Natural Science Foundation of China,No.82101323(to TS)Preferred Foundation of Zhejiang Postdoctors,No.ZJ2021152(to TS).
文摘Parkinson’s disease is a common neurodegenerative disorder that is associated with abnormal aggregation and accumulation of neurotoxic proteins,includingα-synuclein,amyloid-β,and tau,in addition to the impaired elimination of these neurotoxic protein.Atypical parkinsonism,which has the same clinical presentation and neuropathology as Parkinson’s disease,expands the disease landscape within the continuum of Parkinson’s disease and related disorders.The glymphatic system is a waste clearance system in the brain,which is responsible for eliminating the neurotoxic proteins from the interstitial fluid.Impairment of the glymphatic system has been proposed as a significant contributor to the development and progression of neurodegenerative disease,as it exacerbates the aggregation of neurotoxic proteins and deteriorates neuronal damage.Therefore,impairment of the glymphatic system could be considered as the final common pathway to neurodegeneration.Previous evidence has provided initial insights into the potential effect of the impaired glymphatic system on Parkinson’s disease and related disorders;however,many unanswered questions remain.This review aims to provide a comprehensive summary of the growing literature on the glymphatic system in Parkinson’s disease and related disorders.The focus of this review is on identifying the manifestations and mechanisms of interplay between the glymphatic system and neurotoxic proteins,including loss of polarization of aquaporin-4 in astrocytic endfeet,sleep and circadian rhythms,neuroinflammation,astrogliosis,and gliosis.This review further delves into the underlying pathophysiology of the glymphatic system in Parkinson’s disease and related disorders,and the potential implications of targeting the glymphatic system as a novel and promising therapeutic strategy.
基金supported by the National Natural Science Foundation of China(91339113,81270202,81070095 to Xin HongBo)the National Basic Research Program of China(2013CB531103 to Xin HongBo)
文摘Endothelial cell dysfunction is a term which implies the dysregulation of normal endothelial cell functions,including impairment of the barrier functions,control of vascular tone,disturbance of proliferative and migratory capacity of endothelial cells,as well as control of leukocyte trafficking.Endothelial dysfunction is an early step in vascular inflammatory diseases such as atherosclerosis,diabetic vascular complications,sepsis-induced or severe virus infection-induced organ injuries.The expressions of inflammatory cytokines and vascular adhesion molecules induced by various stimuli,such as modified lipids,smoking,advanced glycation end products and bacteria toxin,significantly contribute to the development of endothelial dysfunction.The transcriptional regulation of inflammatory cytokines and vascular adhesion molecules has been well-studied.However,the regulation of those gene expressions at post-transcriptional level is emerging.RNA-binding proteins have emerged as critical regulators of gene expression acting predominantly at the post-transcriptional level in microRNA-dependent or independent manners.This review summarizes the latest insights into the roles of RNA-binding proteins in controlling vascular endothelial cell functions and their contribution to the pathogenesis of vascular inflammatory diseases.
基金This work was supported by National Natural Science Foundation of China(30871403,81561138001)partly supported by the Chinese Academy of Sciences.
文摘Adult stem cells that reside in particular types of tissues are responsible for tissue homeostasis and regeneration.Cellular functions of adult stem cells are intricately related to the gene expression programs in those cells.Past research has demonstrated that regulation of gene expression at the transcriptional level can decisively alter cell fate of stem cells.However,cellular contents of mRNAs are sometimes not equivalent to proteins,the functional units of cells.It is increasingly realized that post-transcriptional and translational regulation of gene expression are also fundamental for stem cell functions.Compared to differentiated somatic cells,effects on cellular status manifested by varied expression of RNA-binding proteins and global protein synthesis have been demonstrated in several stem cell systems.Through the cooperation of both cis-elements of mRNAs and trans-acting RNA-binding proteins that are intimately associated with them,regulation of localization,stability,and translational status of mRNAs directly influences the self-renewal and differentiation of stem cells.Previous studies have uncovered some of the molecular mechanisms that underlie the functions of RNA-binding proteins in stem cells in invertebrate species.However,their roles in adult stem cells in mammals are just beginning to be unveiled.This review highlights some of the RNA-binding proteins that play important functions during the maintenance and differentiation of mouse male germline stem cells,the adult stem cells in the male reproductive organ.
基金Project supported by the Gansu Province Industrial Support Plan (Grant No.2023CYZC-25)the Natural Science Foundation of Gansu Province (Grant No.23JRRA770)the National Natural Science Foundation of China (Grant No.62162040)。
文摘Essential proteins are inseparable in cell growth and survival. The study of essential proteins is important for understanding cellular functions and biological mechanisms. Therefore, various computable methods have been proposed to identify essential proteins. Unfortunately, most methods based on network topology only consider the interactions between a protein and its neighboring proteins, and not the interactions with its higher-order distance proteins. In this paper, we propose the DSEP algorithm in which we integrated network topology properties and subcellular localization information in protein–protein interaction(PPI) networks based on four-order distances, and then used random walks to identify the essential proteins. We also propose a method to calculate the finite-order distance of the network, which can greatly reduce the time complexity of our algorithm. We conducted a comprehensive comparison of the DSEP algorithm with 11 existing classical algorithms to identify essential proteins with multiple evaluation methods. The results show that DSEP is superior to these 11 methods.
文摘Protein-based therapeutics (PPTs) are drugs used to treat a variety of different conditions in the human body by alleviating enzymatic deficiencies, augmenting other proteins and drugs, modulating signal pathways, and more. However, many PPTs struggle from a short half-life due to degradation caused by irreversible protein aggregation in the bloodstream. Currently, the most researched strategies for improving the efficiency and longevity of PPTs are post-translational modifications (PTMs). The goal of our research was to determine which type of PTM increases longevity the most for each of three commonly-used therapeutic proteins by comparing the docking scores (DS) and binding free energies (BFE) from protein aggregation and reception simulations. DS and BFE values were used to create a quantitative index that outputs a relative number from −1 to 1 to show reduced performance, no change, or increased performance. Results showed that methylation was the most beneficial for insulin (p < 0.1) and human growth hormone (p < 0.0001), and both phosphorylation and methylation were somewhat optimal for erythropoietin (p < 0.1 and p < 0.0001, respectively). Acetylation consistently provided the worst benefits with the most negative indices, while methylation had the most positive indices throughout. However, PTM efficacy varied between PPTs, supporting previous studies regarding how each PTM can confer different benefits based on the unique structures of recipient proteins.
基金supported by the grants from the National Natural Science Foundation of China(U2004140)the Henan Provincial Science and Technology Major Project,China(221100110100)。
文摘Hyphal fusion(anastomosis)is a common process serving many important functions at various developmental stages in the life cycle of ascomycetous fungi.However,the biological roles and molecular mechanisms in plant pathogenic fungi were widely unknown.In this study,a hyphal fusion protein FpHam-2 was screened from a T-DNA insertion mutant library of Fusarium pseudograminearum,and FpHam-2 interacts with another 2 hyphal fusion protein homologues FpHam-3 and FpHam-4.Each of these 3 genes deletion mutant revealed in similar defective phenotypes compared with the WT and complemented strains,including reduction in growth rate,defects in hyphal fusion and conidiation,more sensitive for cell membrane,cell wall and oxidative stress responses,and decreased in virulence.The yeast two-hybrid assay was used to identify that FpHam-2 interacts with 3 autophagy-related proteins,including FpAtg3,FpAtg28 and FpAtg33.Furthermore,FpHam-2-deletion mutant showed decreased accumulation of autophagic bodies in hypha.In conclusion,FpHam-2,FpHam-3 and FpHam-4 have an essential role for hyphal fusion and regulating the growth,conidiation and virulence in F.pseudograminearum.
基金supported by the National Science Foundation of China (32171941,31571583)。
文摘Plant calmodulins(CaMs)and calmodulin-like proteins(CMLs)mediate Ca~(2+)signaling in response to abiotic stresses.Manipulation of this signaling in crops could increase stress tolerance.We review methods for detecting Ca~(2+)signals,regulatory roles of Ca Ms and CMLs,binding targets,and Ca~(2+)networks under abiotic stress in organelles.
文摘BACKGROUND Heat shock proteins(HSPs)are molecular chaperones that play an important role in cellular protection against stress events and have been reported to be overex-pressed in many cancers.The prognostic significance of HSPs and their regulatory factors,such as heat shock factor 1(HSF1)and CHIP,are poorly understood.AIM To investigate the relationship between HSP expression and prognosis in esophageal and esophagogastric cancer.METHODS A systematic review was conducted in accordance with PRISMA recommend-ations(PROSPERO:CRD42022370653),on Embase,PubMed,Cochrane,and LILACS.Cohort,case-control,and cross-sectional studies of patients with eso-phagus or esophagogastric cancer were included.HSP-positive patients were compared with HSP-negative,and the endpoints analyzed were lymph node metastasis,tumor depth,distant metastasis,and overall survival(OS).HSPs were stratified according to the HSP family,and the summary risk difference(RD)was calculated using a random-effect model.RESULTS The final selection comprised 27 studies,including esophageal squamous cell carcinoma(21),esophagogastric adenocarcinoma(5),and mixed neoplasms(1).The pooled sample size was 3465 patients.HSP40 and 60 were associated with a higher 3-year OS[HSP40:RD=0.22;95%confidence interval(CI):0.09-0.35;HSP60:RD=0.33;95%CI:0.17-0.50],while HSF1 was associated with a poor 3-year OS(RD=-0.22;95%CI:-0.32 to-0.12).The other HSP families were not associated with long-term survival.HSF1 was associated with a higher probability of lymph node metastasis(RD=-0.16;95%CI:-0.29 to-0.04).HSP40 was associated with a lower probability of lymph node dissemination(RD=0.18;95%CI:0.03-0.33).The expression of other HSP families was not significantly related to tumor depth and lymph node or distant metastasis.CONCLUSION The expression levels of certain families of HSP,such as HSP40 and 60 and HSF1,are associated with long-term survival and lymph node dissemination in patients with esophageal and esophagogastric cancer.
基金supported by the National Natural Science Foundation of China(31970516 and 32372104)the Foundation of Hubei Hongshan Laboratory(2021hszd014).
文摘Cotton provides the most abundant natural fiber for the textile industry.The mature cotton fiber largely consists of secondary cell walls with the highest proportion of cellulose and a small amount of hemicellulose and lignin.To dissect the roles of hemicellulosic polysaccharides during fiber development,four IRREGULAR XYLEM 15(IRX15)genes,GhIRX15-1/-2/-3/-4,were functionally characterized in cotton.These genes encode DUF579 domain-containing proteins,which are homologs of AtIRX15 involved in xylan biosynthesis.The four GhIRX15 genes were predominantly expressed during fiber secondary wall thickening,and the encoded proteins were localized to the Golgi apparatus.Each GhIRX15 gene could restore the xylan deficient phenotype in the Arabidopsis irx15irx15l double mutant.Silencing of GhIRX15s in cotton resulted in shorter mature fibers with a thinner cell wall and reduced cellulose content as compared to the wild type.Intriguingly,GhIRX15-2 and GhIRX15-4 formed homodimers and heterodimers.In addition,the GhIRX15s showed physical interaction with glycosyltransferases GhGT43C,GhGT47A and GhGT47B,which are responsible for synthesis of the xylan backbone and reducing end sequence.Moreover,the GhIRX15s can form heterocomplexes with enzymes involved in xylan modification and side chain synthesis,such as GhGUX1/2,GhGXM1/2 and GhTBL1.These findings suggest that GhIRX15s participate in fiber xylan biosynthesis and modulate fiber development via forming large multiprotein complexes.
基金supported by the National Natural Science Foundation of China (32102605)the Agricultural Science and Technology Innovation Program under Grant (CAAS-ASTIP-2020IAR)the Earmarked Fund for CARS (CARS-44)。
文摘Food allergens are mainly naturally-occurring proteins with immunoglobulin E(IgE)-binding epitopes.Understanding the structural and immunogenic characteristics of allergenic proteins is essential in assessing whether and how food processing techniques reduce allergenicity.We here discuss the impacts of food processing technologies on the modification of physicochemical,structural,and immunogenic properties of allergenic proteins.Detection techniques for characterizing changes in these properties of food allergens are summarized.Food processing helps to reduce allergenicity by aggregating or denaturing proteins,which masks,modifies,or destroys antigenic epitopes,whereas,it cannot eliminate allergenicity completely,and sometimes even improves allergenicity by exposing new epitopes.Moreover,most food processing techniques have been tested on purified food allergens rather than food products due to potential interference of other food components.We provide guidance for further development of processing operations that can decrease the allergenicity of allergenic food proteins without negatively impacting the nutritional profile.