During vegetative development, higher plants continuously form new leaves in regular spatial and temporal patterns. Mutants with abnormal leaf developmental patterns not only provide a great insight into understanding...During vegetative development, higher plants continuously form new leaves in regular spatial and temporal patterns. Mutants with abnormal leaf developmental patterns not only provide a great insight into understanding the regulatory mechanism of plant architecture, but also enrich the ways to its modification by which crop yield could be improved. Here, we reported the characterization of the rice leafy-head2 （lhd2） mutant that exhibits shortened plastochron, dwarfism, reduced tiller number, and failure of phase transition from vegetative to reproductive growth. Anatomical and histological study revealed that the rapid emergence of leaves in lhd2 was resulted from the rapid initiation of leaf primordia whereas the reduced tiller number was a consequence of the suppression of the tiller bud outgrowth. The molecular and genetic analysis showed that LHD2 encodes a putative RNA binding protein with 67% similarity to maize TEl. Comparison of genome-scale expression profiles between wild-type and lhd2 plants suggested that LHD2 may regulate rice shoot development through KNOXand hormone-related genes. The similar phenotypes caused by LHD2 mutation and the conserved expression pattern of LHD2 indicated a conserved mechanism in controlling the temporal leaf initiation in grass.展开更多
The effect of cold stress on the gene expression of cold-inducible RNA-binding protein （CIRP） in the intravital animals has not been reported till now. Compared with their organism cells, there were much more compli...The effect of cold stress on the gene expression of cold-inducible RNA-binding protein （CIRP） in the intravital animals has not been reported till now. Compared with their organism cells, there were much more complicated regulatory mechanisms for cold stress response in the organisms. The BALB/C mice with cold treatment were used as experimental animals for this study. The cDNA of CIRP was firstly cloned from the testis tissues of the BALB/C mice treated by cold stress The results indicated that CIRP in the organisms could be induced at low temperature and may protect the organisms from the cold damage. The amino acid sequence deduced via cDNA clone was 100%, 99.4%, 95.5%, 67.4%, 76.9%, 79.1% and 58.4% identical with that of CIRP in mice, rats, human, bullfrog, Xenopus and axolotl cells, respectively. These results showed that the CIRP was highly conserved in the evolution process and may be involved in various physiological functions. Therefore, this study will establish a systematic model for experiments and provide a new foundation for exploring the molecular mechanisms of human and other animals under cold stress.展开更多
Cold-inducible RNA-binding protein(CIRP) is a kind of RNA binding proteins that plays important roles in many physiological processes. The CIRP has been widely studied in mammals and amphibians since it was first clon...Cold-inducible RNA-binding protein(CIRP) is a kind of RNA binding proteins that plays important roles in many physiological processes. The CIRP has been widely studied in mammals and amphibians since it was first cloned from mammals. On the contrary, there are little reports in teleosts. In this study, the Po CIRP gene of the Japanese flounder was cloned and sequenced. The genomic sequence consists of seven exons and six introns. The putative Po CIRP protein of flounder was 198 amino acid residues long containing the RNA recognition motif(RRM). Phylogenetic analysis showed that the flounder Po CIRP is highly conserved with other teleost CIRPs. The 5' flanking sequence was cloned by genome walking and many transcription factor binding sites were identified. There is a Cp Gs region located in promoter and exon I region and the methylation state is low. Quantitative real-time PCR analysis uncovered that Po CIRP gene was widely expressed in adult tissues with the highest expression level in the ovary. The m RNA of the Po CIRP was maternally deposited and the expression level of the gene was regulated up during the gastrula and neurula stages. In order to gain the information how the protein interacts with m RNA, we performed the modeling of the 3D structure of the flounder Po CIRP. The results showed a cleft existing the surface of the molecular. Taken together, the results indicate that the CIRP is a multifunctional molecular in teleosts and the findings about the structure provide valuable information for understanding the basis of this protein's function.展开更多
Xenopus ZFP36L1 （zinc finger protein 36, C3H type-like 1） belongs to the ZFP36 family of RNA-binding proteins, which contains two characteristic tandem CCCH-type zinc-finger domains. The ZFP36 proteins can bind AU-r...Xenopus ZFP36L1 （zinc finger protein 36, C3H type-like 1） belongs to the ZFP36 family of RNA-binding proteins, which contains two characteristic tandem CCCH-type zinc-finger domains. The ZFP36 proteins can bind AU-rich elements in 3＇ untranslated regions of target mRNAs and promote their turnover. However, the expression and role of ZFP36 genes during neural development in Xenopus embryos remains largely unknown. The present study showed that Xenopus ZFP36L1 was expressed at the dorsal part of the forebrain, forebrain-midbrain boundary, and midbrain-hindbrain boundary from late neurula stages to tadpole stages of embryonic development. Overexpression of XZFP36L1 in Xenopus embryos inhibited neural induction and differentiation, leading to severe neural tube defects. The function of XZP36L1 requires both its zinc finger and C terminal domains, which also affect its subcellular localization. These results suggest that XZFP36L1 is likely involved in neural development in Xenopus and might play an important role in post-transcriptional regulation.展开更多
Cells use various RNA （Ribonucleic Acid） regulatory mechanisms in order to temporally and coordinately influence the rate of protein synthesis. A deeper understanding of the dynamics of RNA regulation can ultimately...Cells use various RNA （Ribonucleic Acid） regulatory mechanisms in order to temporally and coordinately influence the rate of protein synthesis. A deeper understanding of the dynamics of RNA regulation can ultimately bridge the gap between transcriptional control and protein expression. The nonlinear process of RNA-Protein Interaction （RIP）, which can be viewed as the RNA analog of the better-known chromatin immunoprecipitation application （CHIP） plays a crucial role in post-transcriptional regulation of gene expression. While ChIP identifies DNA （Deoxyribonucleic Acid） targets of DNA-binding proteins in their cellular context, RIP can be used to identify specific RNA molecules associated with specific nuclear or cytoplasmic RNA-binding proteins. In this paper, a stochastic model in BioAmbients calculus for the protein synthesis and activation through RIP process is presemed.展开更多
Objective: Mucoepidermoid carcinoma(MEC) is the most common primary malignancy of the salivary glands. Insulin-like growth factor-II m RNA-binding protein-3(IMP3) is an important prognostic factor in some cancers and ...Objective: Mucoepidermoid carcinoma(MEC) is the most common primary malignancy of the salivary glands. Insulin-like growth factor-II m RNA-binding protein-3(IMP3) is an important prognostic factor in some cancers and a tool that differentiates between benign and malignant pancreatic lesions. This study aimed to identify a relationship between the expression of IMP3 and the outcome of salivary gland MEC, as well as to differentiate MEC from pleomorphic adenoma(PA).Methods: Tissue specimens from 70 cases of salivary gland MEC, 40 cases of PA, and 10 cases with normal salivary gland were examined immunohistochemically for IMP3. The association among the expression of IMP3, clinicopathological characteristics and patient's survival was assessed.Results: IMP3 was present in 51.4% of MEC but absent in PA and normal salivary gland tissues. IMP3 expression was associated with age > 60 years, submandibular gland tumors, tumor size > 4 cm, high-grade tumors, lymph node metastasis, involvement of surgical margins, perineural invasion, distant metastasis, advanced TNM stage, tumor relapse, and death(P<0.05). Increased expression of IMP3, tumors of the submandibular gland, and lymph node metastasis were independent prognostic factors of disease-free survival(DFS). In addition, IMP3 was a strong predictor of overall survival(OS) together with distant metastasis and intermediate and high-grade tumors.Conclusions: IMP3 expression is highly important in evaluating the outcome of MEC. IMP3 can be used to differentiate MEC from PA of salivary glands.展开更多
Objective To screen the proteins associated with four-and-a-half LIM domains 3(FHL3) 3' untranslated region(3'UTR) in glioma cells. Methods Western blot was adopted to detect the regulatory effect of poly(C)-b...Objective To screen the proteins associated with four-and-a-half LIM domains 3(FHL3) 3' untranslated region(3'UTR) in glioma cells. Methods Western blot was adopted to detect the regulatory effect of poly(C)-binding protein 2(PCBP2) on FHL3. Biotin pull-down and sliver staining were employed to screen and verify the candidate binding proteins of FHL3 3'UTR. Then liquid chromatography-tandem mass spectrometry(LC-MS/MS) and molecule annotation system were used to identify and analyze the candidate binding proteins. Immunoprecipitation was conducted to study the interaction between PCBP2 and polypyrimidine tract-binding protein 1(PTBP1), a binding protein identified by LC-MS/MS. Results PCBP2 could bind to FHL3 mRNA 3'UTR-A and inhibited the expression of FHL3 in T98 G glioms cells. 22 candidate binding proteins were identified. Among them, there were 11 RNA binding proteins, including PCBP2. PTBP1 associated with FHL3 mRNA 3'UTR and interacted with PCBP2 protein. Conclusion PCBP2 and PTBP1 can both associate with FHL3 mRNA 3'UTR through forming a protein complex.展开更多
Long non-coding RNAs(lncRNAs),which represent a new frontier in molecular biology,play important roles in regulating gene expression at epigenetic,transcriptional and post-transcriptional levels.More and more lncRNAs ...Long non-coding RNAs(lncRNAs),which represent a new frontier in molecular biology,play important roles in regulating gene expression at epigenetic,transcriptional and post-transcriptional levels.More and more lncRNAs have been found to play important roles in normal cell physiological activities,and participate in the development of varieties of tumors and other diseases.Previously,we have only been able to determine the function of lncRNAs through multiple mechanisms,including genetic imprinting,chromatin remodeling,splicing regulation,mRNA decay,and translational regulation.Application of technological advances to research into the function of lncRNAs is extremely important.The major tools for exploring lncRNAs include microarrays,RNA sequencing(RNA-seq),Northern blotting,real-time quantitative reverse transcription-polymerase chain reaction(qRT-PCR),fluorescence in situ hybridization(FISH),RNA interference(RNAi),RNA-binding protein immunoprecipitation(RIP),chromatin isolation by RNA purification(ChIRP),crosslinking-immunopurification(CLIP),and bioinformatic prediction.In this review,we highlight the functions of lncRNAs,and advanced methods to research lncRNA-protein interactions.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 pervasive transcription of the genome creates many types of non-coding RNAs(nc RNAs).However,we know very little regarding the functions and the regulatory mechanisms of these nc RNAs.Exploring the interactions of...The pervasive transcription of the genome creates many types of non-coding RNAs(nc RNAs).However,we know very little regarding the functions and the regulatory mechanisms of these nc RNAs.Exploring the interactions of RNA and RNA binding proteins(RBPs) is vital because it can allow us to truly understand how these nc RNAs behave in vivo.High-throughput sequencing of RNA isolated by cross-linking immunoprecipitation(HITS-CLIP or CLIP-seq) and its variants have been successfully used as systemic techniques to study RBP binding sites.In this review,we will explain the major differences between the CLIP techniques,summarize successful applications of these techniques,discuss limitations of CLIP,present some suggested solutions and project their promising future roles in studying the RNA world.展开更多
Elucidating protein translational regulation is crucial for understanding cellular function and drug development.A key molecule in protein translation is ribosome,which is a super-molecular complex extensively studied...Elucidating protein translational regulation is crucial for understanding cellular function and drug development.A key molecule in protein translation is ribosome,which is a super-molecular complex extensively studied for more than a half century.The structure and dynamics of ribosome complexes were resolved recently thanks to the development of X-ray crystallography,Cryo-EM,and single molecule biophysics.Current studies of the ribosome have shown multiple functional states,each with a unique conformation.In this study,we analyzed the RNA-protein distances of ribosome(2.5 MDa)complexes and compared these changes among different ribosome complexes.We found that the RNA-protein distance is significantly correlated with the ribosomal functional state.Thus,the analysis of RNA-protein binding distances at important functional sites can distinguish ribosomal functional states and help understand ribosome functions.In particular,the mechanism of translational attenuation by nascent peptides and antibiotics was revealed by the conformational changes of local functional sites.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
Ribosomal proteins （RPs）, the essential components of the ribosome, are a family of RNA-binding proteins, which play prime roles in ribosome biogenesis and protein translation. Recent studies revealed that RPs have ...Ribosomal proteins （RPs）, the essential components of the ribosome, are a family of RNA-binding proteins, which play prime roles in ribosome biogenesis and protein translation. Recent studies revealed that RPs have additional extra-ribosomal func- tions, independent of protein biosynthesis, in regulation of diverse cellular processes. Here, we review recent advances in our understanding of how RPs regulate apoptosis, cell cycle arrest, cell proliferation, neoplastic transformation, cell migration and invasion, and tumorigenesis through both MDM2/p53-dependent and p53-independent mechanisms. We also discuss the roles of RPs in the maintenance of genome integrity via modulating DNA damage response and repair. We further discuss mutations or deletions at the somatic or gennline levels of some RPs in human cancers as well as in patients of Diamond-Blackfan ane- mia and 5q- syndrome with high susceptibility to cancer development. Moreover, we discuss the potential clinical application, based upon abnormal levels of RPs, in biomarker development for early diagnosis and/or prognosis of certain human cancers. Finally, we discuss the pressing issues in the field as future perspectives for better understanding the roles of RPs in human cancers to eventually benefit human health.展开更多
文摘During vegetative development, higher plants continuously form new leaves in regular spatial and temporal patterns. Mutants with abnormal leaf developmental patterns not only provide a great insight into understanding the regulatory mechanism of plant architecture, but also enrich the ways to its modification by which crop yield could be improved. Here, we reported the characterization of the rice leafy-head2 （lhd2） mutant that exhibits shortened plastochron, dwarfism, reduced tiller number, and failure of phase transition from vegetative to reproductive growth. Anatomical and histological study revealed that the rapid emergence of leaves in lhd2 was resulted from the rapid initiation of leaf primordia whereas the reduced tiller number was a consequence of the suppression of the tiller bud outgrowth. The molecular and genetic analysis showed that LHD2 encodes a putative RNA binding protein with 67% similarity to maize TEl. Comparison of genome-scale expression profiles between wild-type and lhd2 plants suggested that LHD2 may regulate rice shoot development through KNOXand hormone-related genes. The similar phenotypes caused by LHD2 mutation and the conserved expression pattern of LHD2 indicated a conserved mechanism in controlling the temporal leaf initiation in grass.
基金This research was supported by National Postdoctoral Science Foundation of China （No. 20060390241）.
文摘The effect of cold stress on the gene expression of cold-inducible RNA-binding protein （CIRP） in the intravital animals has not been reported till now. Compared with their organism cells, there were much more complicated regulatory mechanisms for cold stress response in the organisms. The BALB/C mice with cold treatment were used as experimental animals for this study. The cDNA of CIRP was firstly cloned from the testis tissues of the BALB/C mice treated by cold stress The results indicated that CIRP in the organisms could be induced at low temperature and may protect the organisms from the cold damage. The amino acid sequence deduced via cDNA clone was 100%, 99.4%, 95.5%, 67.4%, 76.9%, 79.1% and 58.4% identical with that of CIRP in mice, rats, human, bullfrog, Xenopus and axolotl cells, respectively. These results showed that the CIRP was highly conserved in the evolution process and may be involved in various physiological functions. Therefore, this study will establish a systematic model for experiments and provide a new foundation for exploring the molecular mechanisms of human and other animals under cold stress.
基金supported by the National High Technology R&D Program of China (2012AA10A402)the National Natural Science Foundation of China (31172385)
文摘Cold-inducible RNA-binding protein(CIRP) is a kind of RNA binding proteins that plays important roles in many physiological processes. The CIRP has been widely studied in mammals and amphibians since it was first cloned from mammals. On the contrary, there are little reports in teleosts. In this study, the Po CIRP gene of the Japanese flounder was cloned and sequenced. The genomic sequence consists of seven exons and six introns. The putative Po CIRP protein of flounder was 198 amino acid residues long containing the RNA recognition motif(RRM). Phylogenetic analysis showed that the flounder Po CIRP is highly conserved with other teleost CIRPs. The 5' flanking sequence was cloned by genome walking and many transcription factor binding sites were identified. There is a Cp Gs region located in promoter and exon I region and the methylation state is low. Quantitative real-time PCR analysis uncovered that Po CIRP gene was widely expressed in adult tissues with the highest expression level in the ovary. The m RNA of the Po CIRP was maternally deposited and the expression level of the gene was regulated up during the gastrula and neurula stages. In order to gain the information how the protein interacts with m RNA, we performed the modeling of the 3D structure of the flounder Po CIRP. The results showed a cleft existing the surface of the molecular. Taken together, the results indicate that the CIRP is a multifunctional molecular in teleosts and the findings about the structure provide valuable information for understanding the basis of this protein's function.
基金Foundation items： This work was supported by National Natural Science Foundation of China （90919039 C120106） Acknowledgements We thank the National Institute for Basic Biology, Japan, for the X1073h24 clone.
文摘Xenopus ZFP36L1 （zinc finger protein 36, C3H type-like 1） belongs to the ZFP36 family of RNA-binding proteins, which contains two characteristic tandem CCCH-type zinc-finger domains. The ZFP36 proteins can bind AU-rich elements in 3＇ untranslated regions of target mRNAs and promote their turnover. However, the expression and role of ZFP36 genes during neural development in Xenopus embryos remains largely unknown. The present study showed that Xenopus ZFP36L1 was expressed at the dorsal part of the forebrain, forebrain-midbrain boundary, and midbrain-hindbrain boundary from late neurula stages to tadpole stages of embryonic development. Overexpression of XZFP36L1 in Xenopus embryos inhibited neural induction and differentiation, leading to severe neural tube defects. The function of XZP36L1 requires both its zinc finger and C terminal domains, which also affect its subcellular localization. These results suggest that XZFP36L1 is likely involved in neural development in Xenopus and might play an important role in post-transcriptional regulation.
文摘Cells use various RNA （Ribonucleic Acid） regulatory mechanisms in order to temporally and coordinately influence the rate of protein synthesis. A deeper understanding of the dynamics of RNA regulation can ultimately bridge the gap between transcriptional control and protein expression. The nonlinear process of RNA-Protein Interaction （RIP）, which can be viewed as the RNA analog of the better-known chromatin immunoprecipitation application （CHIP） plays a crucial role in post-transcriptional regulation of gene expression. While ChIP identifies DNA （Deoxyribonucleic Acid） targets of DNA-binding proteins in their cellular context, RIP can be used to identify specific RNA molecules associated with specific nuclear or cytoplasmic RNA-binding proteins. In this paper, a stochastic model in BioAmbients calculus for the protein synthesis and activation through RIP process is presemed.
文摘Objective: Mucoepidermoid carcinoma(MEC) is the most common primary malignancy of the salivary glands. Insulin-like growth factor-II m RNA-binding protein-3(IMP3) is an important prognostic factor in some cancers and a tool that differentiates between benign and malignant pancreatic lesions. This study aimed to identify a relationship between the expression of IMP3 and the outcome of salivary gland MEC, as well as to differentiate MEC from pleomorphic adenoma(PA).Methods: Tissue specimens from 70 cases of salivary gland MEC, 40 cases of PA, and 10 cases with normal salivary gland were examined immunohistochemically for IMP3. The association among the expression of IMP3, clinicopathological characteristics and patient's survival was assessed.Results: IMP3 was present in 51.4% of MEC but absent in PA and normal salivary gland tissues. IMP3 expression was associated with age > 60 years, submandibular gland tumors, tumor size > 4 cm, high-grade tumors, lymph node metastasis, involvement of surgical margins, perineural invasion, distant metastasis, advanced TNM stage, tumor relapse, and death(P<0.05). Increased expression of IMP3, tumors of the submandibular gland, and lymph node metastasis were independent prognostic factors of disease-free survival(DFS). In addition, IMP3 was a strong predictor of overall survival(OS) together with distant metastasis and intermediate and high-grade tumors.Conclusions: IMP3 expression is highly important in evaluating the outcome of MEC. IMP3 can be used to differentiate MEC from PA of salivary glands.
基金Supported by Peking Union Medical College Youth Fundthe Fundamental Research Funds for the Central Universities(3332013052)
文摘Objective To screen the proteins associated with four-and-a-half LIM domains 3(FHL3) 3' untranslated region(3'UTR) in glioma cells. Methods Western blot was adopted to detect the regulatory effect of poly(C)-binding protein 2(PCBP2) on FHL3. Biotin pull-down and sliver staining were employed to screen and verify the candidate binding proteins of FHL3 3'UTR. Then liquid chromatography-tandem mass spectrometry(LC-MS/MS) and molecule annotation system were used to identify and analyze the candidate binding proteins. Immunoprecipitation was conducted to study the interaction between PCBP2 and polypyrimidine tract-binding protein 1(PTBP1), a binding protein identified by LC-MS/MS. Results PCBP2 could bind to FHL3 mRNA 3'UTR-A and inhibited the expression of FHL3 in T98 G glioms cells. 22 candidate binding proteins were identified. Among them, there were 11 RNA binding proteins, including PCBP2. PTBP1 associated with FHL3 mRNA 3'UTR and interacted with PCBP2 protein. Conclusion PCBP2 and PTBP1 can both associate with FHL3 mRNA 3'UTR through forming a protein complex.
基金supported by the National Basic Research Program of China(2010CB912801,2013CB910801)National High Technology Research and Development Program of China(2012AA022501)National Natural Science Foundation of China(31070702,31270836)
文摘Long non-coding RNAs(lncRNAs),which represent a new frontier in molecular biology,play important roles in regulating gene expression at epigenetic,transcriptional and post-transcriptional levels.More and more lncRNAs have been found to play important roles in normal cell physiological activities,and participate in the development of varieties of tumors and other diseases.Previously,we have only been able to determine the function of lncRNAs through multiple mechanisms,including genetic imprinting,chromatin remodeling,splicing regulation,mRNA decay,and translational regulation.Application of technological advances to research into the function of lncRNAs is extremely important.The major tools for exploring lncRNAs include microarrays,RNA sequencing(RNA-seq),Northern blotting,real-time quantitative reverse transcription-polymerase chain reaction(qRT-PCR),fluorescence in situ hybridization(FISH),RNA interference(RNAi),RNA-binding protein immunoprecipitation(RIP),chromatin isolation by RNA purification(ChIRP),crosslinking-immunopurification(CLIP),and bioinformatic prediction.In this review,we highlight the functions of lncRNAs,and advanced methods to research lncRNA-protein interactions.
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.
基金supported by the National Natural Science Foundation of China(31200593,31230042)the Guangdong Natural Science Foundation (S2011040001760)+1 种基金the Fundamental Research Funds for the Central Universities (13lgpy40)the National Basic Research Program of China (2011CB811300)
文摘The pervasive transcription of the genome creates many types of non-coding RNAs(nc RNAs).However,we know very little regarding the functions and the regulatory mechanisms of these nc RNAs.Exploring the interactions of RNA and RNA binding proteins(RBPs) is vital because it can allow us to truly understand how these nc RNAs behave in vivo.High-throughput sequencing of RNA isolated by cross-linking immunoprecipitation(HITS-CLIP or CLIP-seq) and its variants have been successfully used as systemic techniques to study RBP binding sites.In this review,we will explain the major differences between the CLIP techniques,summarize successful applications of these techniques,discuss limitations of CLIP,present some suggested solutions and project their promising future roles in studying the RNA world.
基金partially supported by National Institute of Health(R21/R33-GM078601 and R01-GM100701)National Science Foundation(MCB-1151343)in the US
文摘Elucidating protein translational regulation is crucial for understanding cellular function and drug development.A key molecule in protein translation is ribosome,which is a super-molecular complex extensively studied for more than a half century.The structure and dynamics of ribosome complexes were resolved recently thanks to the development of X-ray crystallography,Cryo-EM,and single molecule biophysics.Current studies of the ribosome have shown multiple functional states,each with a unique conformation.In this study,we analyzed the RNA-protein distances of ribosome(2.5 MDa)complexes and compared these changes among different ribosome complexes.We found that the RNA-protein distance is significantly correlated with the ribosomal functional state.Thus,the analysis of RNA-protein binding distances at important functional sites can distinguish ribosomal functional states and help understand ribosome functions.In particular,the mechanism of translational attenuation by nascent peptides and antibiotics was revealed by the conformational changes of local functional sites.
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supported by the National Natural Science Foundation of China (81572708, 31501129 to Xiufang Xiong 81572718 to Yi Sun)
文摘Ribosomal proteins （RPs）, the essential components of the ribosome, are a family of RNA-binding proteins, which play prime roles in ribosome biogenesis and protein translation. Recent studies revealed that RPs have additional extra-ribosomal func- tions, independent of protein biosynthesis, in regulation of diverse cellular processes. Here, we review recent advances in our understanding of how RPs regulate apoptosis, cell cycle arrest, cell proliferation, neoplastic transformation, cell migration and invasion, and tumorigenesis through both MDM2/p53-dependent and p53-independent mechanisms. We also discuss the roles of RPs in the maintenance of genome integrity via modulating DNA damage response and repair. We further discuss mutations or deletions at the somatic or gennline levels of some RPs in human cancers as well as in patients of Diamond-Blackfan ane- mia and 5q- syndrome with high susceptibility to cancer development. Moreover, we discuss the potential clinical application, based upon abnormal levels of RPs, in biomarker development for early diagnosis and/or prognosis of certain human cancers. Finally, we discuss the pressing issues in the field as future perspectives for better understanding the roles of RPs in human cancers to eventually benefit human health.
