MicroRNA-regulated viral vectors for gene therapy

Safe and effective gene therapy approaches require targeted tissue-specific transfer of a therapeutic transgene.Besides traditional approaches, such as transcriptional and transductional targeting, micro RNA-dependent posttranscriptional suppression of transgene expression has been emerging as powerful new technology to increase the specificity of vector-mediated transgene expression. Micro RNAs are small non-coding RNAs and often expressed in a tissue-, lineage-, activation- or differentiation-specific pattern. They typically regulate gene expression by binding to imperfectly complementary sequences in the 3' untranslated region(UTR) of the m RNA. To control exogenous transgene expression, tandem repeats of artificial micro RNA target sites are usually incorporated into the 3' UTR of the transgene expression cassette, leading to subsequent degradation of transgene m RNA in cel s expressing the corresponding micro RNA. This targeting strategy, first shown for lentiviral vectors in antigen presenting cells, has now been used for tissue-specific expression of vector-encoded therapeutic transgenes, to reduce immune response against the transgene, to control virus tropism for oncolytic virotherapy, to increase safety of live attenuated virus vaccines and to identify and select cell subsets for pluripotent stem cell therapies, respectively. This review provides an introduction into the technical mechanism underlying micro RNA-regulation, highlights new developments in this field and gives an overview of applications of micro RNA-regulated viral vectors for cardiac, suicide gene cancer and hematopoietic stem cell therapy, as well as for treatment of neurological and eye diseases.

HCV-RNA positivity in peripheral blood mononuclear cells of patients with chronic HCV-infection: does it really mean viral replication?

AIM: To analyze the association of HCV-RNA with peripheral blood mononuclear cells (PBMC) and to answer the question whether HCV-RNA positivity in PBMC is due to viral replication. METHODS: HCV-RNA was monitored in serum and PBMC preparations from 15 patients with chronic HCV infection before, during and after an IFN-alpha therapy using a nested RT/PCR technique. In a second approach, PBMC from healthy donors were incubated in HCV positive plasma. RESULTS: In the IFN-alpha responding patients,HCV-RNA disappeared first from total RNA preparations of PBMC and then from serum. In contrast, in relapsing patients, HCV-RNA reappeared first in serum and then in PBMC. A quantitative analysis of the HCV-RNA concentration in serum was performed before and after transition from detectable to non detectable HCV-RNA in PBMC-RNA and vice versa. When HCV-RNA was detectable in PBMC preparations, the HCV concentration in serum was significantly higher than the serum HCV-RNA concentration when HCV-RNA in PBMC was not detectable. Furthermore, at no time during the observation period was HCV specific RNA observed in PBMC, if HCV-RNA in serum was under the detection limit. Incubation of PBMC from healthy donors with several dilutions of HCV positive plasma for two hours showed a concentration dependent PCR positivity for HCV-RNA in reisolated PBMC. CONCLUSION: The detectability of HCV-RNA in total RNA from PBMC seems to depend on the HCV concentration in serum. Contamination or passive adsorption by circulating virus could be the reason for detection of HCV-RNA in PBMC preparations of chronically infected patients.

Structure-function relationship in viral RNA genomes: The case of hepatitis C virus

The acquisition of a storage information system beyond the nucleotide sequence has been a crucial issue for the propagation and dispersion of RNA viruses. This system is composed by highly conserved, complex structural units in the genomic RNA, termed functional RNA domains. These elements interact with other regions of the viral genome and/or proteins to direct viral translation, replication and encapsidation. The genomic RNA of the hepatitis C virus(HCV) is a good model for investigating about conserved structural units. It contains functional domains, defined by highly conserved structural RNA motifs, mostly located in the 5'-untranslatable regions(5'UTRs) and 3'UTR, but also occupying long stretches of the coding sequence. Viral translation initiation is mediated by an internal ribosome entry site located at the 5' terminus of the viral genome and regulated by distal functional RNA domains placed at the 3' end. Subsequent RNA replication strongly depends on the 3'UTR folding and is also influenced by the 5' end of the HCV RNA. Further increase in the genome copy number unleashes the formation of homodimers by direct interaction of two genomic RNA molecules, which are finally packed and released to the extracellular medium. All these processes, as well as transitions between them, are controlled by structural RNA elements that establish a complex, direct and long-distance RNARNA interaction network. This review summarizes current knowledge about functional RNA domains within the HCV RNA genome and provides an overview of the control exerted by direct, long-range RNA-RNA contacts for the execution of the viral cycle.

RNAi,a new therapeutic strategy against viral infection

RNA interference (RNAi) is an adaptive defense mechanism triggered by double-stranded RNA (dsRNA). It is a powerful reverse genetic tool that has been widely employed to silence gene expression in mammalian and human cells.RNAi-based gene therapies, especially in viral diseases have become more and more interesting and promising. Recently,small interfering RNA (siRNA) can be used to protect host from viral infection, inhibit the expression of viral antigen and accessory genes, control the transcription and replication of viral genome, hinder the assembly of viral particles, and display influences in virus-host interactions. In this review, we attempt to present recent progresses of this breakthrough technology in the above fields and summarize the possibilities of siRNA-based drugs.

非编码RNA在肺纤维化过程中的调控作用

背景:截至目前,肺纤维化的发病机制不明,治疗手段或者药物有限。大量研究发现,非编码RNA在肺纤维化的发生发展过程中发挥重要作用。目的:综述近年来非编码RNA在肺纤维化发病机制中的调控作用,深入了解肺纤维化的发病机制。方法:由第一作者应用计算机检索2000-2024年出版的文献,以“非编码RNA,微小RNA,长链非编码RNA,环状RNA,肺纤维化,综述”等为中文检索词检索中国知网、万方和维普数据库;以“ncRNA,miRNA,lncRNA,circRNA,Pulmonary fibrosis,review”等为英文检索词检索PubMed数据库,按照入选标准最终共纳入65篇文献进行综述。结果与结论:肺纤维化作为一种慢性且通常致命的肺部疾病,不仅可能自发产生,也可能是其他疾病的继发结果,主要特点是肺部间质中细胞外基质的异常增生和大量积累。非编码RNA是指由基因组转录出来的RNA分子,这些RNA分子并不涉及蛋白质的编码过程,凭借其调节能力已成为各种生物学现象中的一线分子参与者之一。非编码RNA在肺纤维化的发病机制中扮演着关键角色,微小RNA(miRNA)、长链非编码RNA(lncRNA)和环状RNA(circRNA)可以通过影响基因表达、转录后修饰以及细胞间的信号传导,参与到肺纤维化的发展过程中,为后续探索肺纤维化疾病的具体分子发生机制提供了新方向,为研发肺纤维化疾病的新靶向药物提供了理论依据及新思路。

The Biochemical Impact by Covalent Shielding of the Anionic Oxygen of the Phosphate Group in DNA and RNA as Methylated Phosphotriester Linkage on the Inhibition of DNA Duplication and on HIV-1 RNA Viral Infectivity Has Been Seriously Overlooked

With the help of model experiments, we are able to offer a detailed proposal for the inhibition of DNA duplication and no inhibition of RNA viral infectivity. As a backbone, we introduced methyl phosphotriester (MPTE). Duplex formation according to the traditional Watson and Crick base-pairing: [(MPTE)n−1 DNA] * DNA and [(MPTE)n−1 DNA] * RNA, where n = number of DNA and RNA bases. However, in the latter case, inhibition is obtained by reduction of the number of MPTE linkages, as is confirmed with model experiments and under biological conditions with micro (mi)RNA substrates. The latter results have recently been published. One or more single MPTEs are disseminated over different places of DNA without neighbour MPTEs (Prof. Wen-Yih Chen and his group, Taiwan).

Non-coding RNAs in acute ischemic stroke:from brain to periphery

Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and disability.Accurate predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain undetermined.With innovations in high-throughput gene sequencing analysis,many aberrantly expressed non-coding RNAs(ncRNAs)in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental models.Differentially expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes,leading to neuroprotection or deterioration,thus ncRNAs can serve as therapeutic targets in acute ischemic stroke.Moreover,distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.In particular,ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic stroke.In this review,we consolidate the latest progress of research into the roles of ncRNAs(microRNAs,long ncRNAs,and circular RNAs)in the pathological processes of acute ischemic stroke–induced brain damage,as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.Findings from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.

Reverse genetics: Unlocking the secrets of negative sense RNA viral pathogens

Negative-sense RNA viruses comprise several zoonotic pathogens that mutate rapidly and frequently emerge in people including Influenza, Ebola, Rabies, Hendra and Nipah viruses. Acute respiratory distress syndrome, encephalitis and vasculitis are common disease outcomes in people as a result of pathogenic viral infection, and are also associated with high case fatality rates. Viral spread from exposure sites to systemic tissues and organs is mediated by virulence factors, including viral attachment glycoproteins and accessory proteins, and their contribution to infection and disease have been delineated by reverse genetics; a molecular approach that enables researchers to experimentally produce recombinant and reassortant viruses from cloned cD NA. Through reverse genetics we have developed a deeper understanding of virulence factors key to disease causation thereby enabling development of targeted antiviral therapies and well-defined live attenuated vaccines. Despite the value of reverse genetics for virulence factor discovery, classical reverse genetic approaches may not provide sufficient resolution for characterization of heterogeneous viral populations, because current techniques recover clonal virus, representing a consensus sequence. In this review the contribution of reverse genetics to virulence factor characterization is outlined, while the limitation of the technique is discussed withreference to new technologies that may be utilized to improve reverse genetic approaches.

Intracellular Transport of HIV-1 Matrix Protein Associated with Viral RNA

HIV-1 matrix protein (MA) is a multifunctional structural protein localized on N terminus of Gag precursor p55. MA participates in HIV-1 assembly as membranotropic part of Gag precursor as well as an individual protein spliced from Gag early in infection. MA is found in the nuclei of infected cells and in plasma membrane, the site of virus assembly, in association with viral genome RNA. MA mutated variant M4 which contains two changed amino acids in N-terminal regions is also associated with viral RNA, but it is localized in the nuclear and cytoskeleton fractions but not in the plasma membrane suggesting that the mutant is deprived of membranotropic signal and “sticks” in the nuclei an d cytoskeleton, its previous location sites. These data allow suggesting that MA involved into transmission of viral RNA is transported to plasma membrane by cytoskeleton.

Small RNA deep sequencing reveals the presence of multiple viral infections in cucurbit crops in Guangdong,China

Viral diseases are among the most critical damaging factors that impose a global threat to the cucurbit industry.China is the world’s leading country for the production and consumption of cucurbits.Guangdong,a province in southern China dominated by the tropical and subtropical climate,favors the survival of different plant viruses and their vectors.Five main cucurbit crops showing various disease symptoms were surveyed and collected to identify viruses infecting cucurbits in Guangdong during 2018–2020.In the field,the incidence ranged from 5-30%,or even 60-100% in the case of severely infected cucurbits.A total of 357 symptomatic samples were collected and subsequently screened for cucurbit viruses by small RNA deep sequencing and assembly(sRSA).Seventeen virus species belonging to 10 genera were identified in the five main cucurbit crops.The most common viruses were papaya ringspot virus(PRSV;Potyvirus),zucchini tigre mosaic virus(ZTMV;Potyvirus),zucchini yellow mosaic virus(ZYMV;Potyvirus),and watermelon silver mottle virus(WSMoV;Orthotospovirus),with infection rates of 24.4,19.0,17.1,and 14.3%,respectively.Notably,the most prevalent viruses were melon yellow spot orthotospovirus(MYSV)in cucumber,PRSV in squash,cucumber green mottle mosaic virus(CGMMV;Tobamovirus)in bottle gourd,WSMoV in white gourd,and ZYMV in luffa.Mixed infections were prevalent,and the types of mixed infections varied substantially in different cucurbit crops.Moreover,the full-length nucleotide sequences of watermelon green mottle mosaic virus(WGMMV),CGMMV,and watermelon virus A(WVA;Wamavirus)identified in bottle gourd were cloned and analyzed.This study is the first reporting WGMMV infecting bottle gourd in China mainland.In summary,the results demonstrate that in Guangdong,the most prevalent viruses belong to potyviruses,orthotospoviruses,and tobamoviruses groups.The findings will facilitate agricultural researchers and farmers to plan and implement effective disease control strategies aiming at timely detection and management of cucurbit-infecting viral pathogens.

Investigation on Viral Pathogens in <i>Vitis vinifera</i>from Four Production Bases in Hangzhou Vicinity of China by sRNAseq and Molecular Validation

This is the first systematic investigation of viral pathogens in Vitis vinifera from Hangzhou vicinity of China. About 7 viruses and 5 viroids were annotated from four production bases “Dushicun”, “Wangjiayuan”, “Xiajiangcun”, and “Yangducun” covering 15 cultivars through sRNAseq technique. At least 3 viruses—grapevine leaf roll-associated virus 3 (GLRaV-3), grapevine fleck virus (GFkV) and grapevine geminivirus A (GGVA), and 4 viroids—hop stunt viroid (HSVd), citrus viroid II (CVd-II), grapevine yellow speckle viroid 1 (GYSVd-1) and grapevine yellow speckle viroid 2 (GYSVd-2) infected all four bases. “Yangducun” base showed 11, the most infected pathogens. GYSVd-1 showed the highest accumulation in host of Wangjiayuan base. The main infected pathogens were verified by reverse-transcription polymerase chain reaction (RT-PCR) technique, the detected rate reached to 85% - 100%. The results provide an important basis for effective and precise detection of viral diseases in the area and for the virus-free cultivation in future.

KRT18与mRNA及长链非编码RNA互作调控椎间盘髓核细胞损伤的机制

背景:椎间盘中差异表达的RNA结合蛋白在椎间盘退变中发挥着关键作用,其中RNA结合蛋白KRT18水平的降低与椎间盘退行性病变相关,但其在椎间盘髓核细胞中的具体作用尚未完全确定。目的:探讨KRT18与mRNA及长链非编码RNA结合互作对椎间盘髓核细胞的影响及机制。方法:对因腰部骨折或椎间盘退行性病变而接受椎间融合术的患者进行人体髓核组织取样获得正常髓核细胞和退变髓核细胞,并进行iRIP-seq、功能富集分析以及DNA微阵列分析,随后根据分析结果在髓核细胞中敲低KRT18,通过蛋白免疫印迹及qRt-PCR在蛋白和RNA水平检测相关基因水平的表达。结果与结论:通过iRIP-seq分析发现GUAAUC和AGCCUC序列中存在大量的KRT18结合位点,表明KRT18可参与调控RNA的转录、翻译、稳定性或在细胞信号传导途径中发挥作用。其能够与成熟的mRNA稳定结合,其中表达较高的基因包括CRLF1及IGFBP4等,同时与其结合的长链非编码RNA的峰值基因包括SNHG25、SNHG12、NEAT1、USP32、EIF4A2和CDH4,这些基因多涉及细胞凋亡、炎症等多种生物过程,并且能介导细胞外基质代谢的相关通路,KRT18能够调控它们的稳定性、转运、翻译、剪接等多个方面的功能,进而影响基因的表达和细胞功能。实验结果验证了在髓核细胞中敲低KRT18,细胞外基质代谢水平被抑制出现失衡,导致体外椎间盘退变。该研究首次从KRT18与mRNA及长链非编码RNA结合的角度探讨其调控机制,并推测了KRT18在椎间盘退变发病机制中的潜在功能,为今后KRT18关键功能的研究奠定了基础。

Snapshots of a Viral RNA Polymerase Switching Gears from Transcription Initiation to Elongation

During transcription initiation,RNA polymerase binds tightly to the promoter DNA defining the start of transcription,transcribes comparatively slowly,and frequently releases short transcripts(3-8 nucleotides)in a process called abortive cycling.Transitioning to elongation,the second phase of transcription,the polymerase dissociates from the promoter while RNA synthesis continues.Elongation is characterized by higher rates of transcription and tight binding to the RNA transcript.The RNA polymerase from enterophage T7 (T7 RNAP) has been used as a model to understand the mechanism of transcription in general,and the transition from initiation to elongation specifically.This single-subunit enzyme undergoes dramatic conformational changes during this transition to support the changing requirements of nucleic acid interactions while continuously maintaining polymerase function.Crystal structures,available of multiple stages of the initiation complex and of the elongation complex,combined with biochemical and biophysical data,offer molecular detail of the transition.Some of the crystal structures contain a variant of T7 RNAP where proline 266 is substituted by leucine.This variant shows less abortive products and altered timing of transition,and is a valuable tool to study these processes.The structural transitions from early to late initiation are well understood and are consistent with solution data.The timing of events and the structural intermediates in the transition from late initiation to elongation are less well understood,but the available data allows one to formulate testable models of the transition to guide further research.

In situ hybridization detection of persistent infection and viral RNA distribution in laboratory rats with hemorrhagic fever with renal syndrome virus

Digoxigenin-labelled Hantaan specific cDNA probes were used in the present study for in situ hybridization detection of hemorrhagic fever with renal syndrome virus(HFRSV) persistent infection and viral RNA distribution in naturally infected laboratory rat

HIV-1 RNA Viral Load, CD4 Count and Some Haematological Parameters of People Living with HIV in the Enugu Metropolis

Background: It is widely known that the human immune-deficiency virus (HIV) induces biochemical and physiological changes in affected persons. Consequently, the overall aim of this study was to evaluate the HIV-1 RNA viral load, CD4 count, and certain haematological parameters among HIV treatment-na?ve subjects in the Enugu metropolis of Nigeria. Materials and Methods: A total of 252 HIV-infected, ART-native subjects (≥18) attending the University of Nigeria Teaching Hospital (UNTH) in Ituku-Ozalla, Enugu were recruited for this study and were made up of 157 (62.3%) females and 95 (37.7%) males. A total of 250 HIV-negative subjects were used as control subjects (100 males and 150 females). Blood samples were collected from all the participants and their HIV-1 status was confirmed by an immunoblot confirmatory test. Their haematological parameters and CD4 count were evaluated, while the HIV-1 viral load was only assessed on confirmed HIV-positive subjects. Results: There was female predominance (62.3%) among these HIV-positive subjects. The mean age of HIV-positive subjects was 39.16 ± 10.08 years while the mean age of the control subjects was 34.8 ± 8.6 years. The age group of 31 - 40 years (102/252 (40.5%)) constituted most of the test subjects. The total white blood cells (TWBC) (6.05 ± 5.46), lymphocyte counts (36 ± 14), haemoglobin concentrations (Hb) (9.85 ± 7.36) and the CD4 counts (242 ± 228) of the HIV-infected subjects showed a significant difference when compared with their control counterpart values of TWBC (4.5 ± 0.568), lymphocytes (39.67 ± 8.2), Hb (13.48 ± 1.5), and CD4 counts (807 ± 249) (p 0.05). Anaemia, lymphocytopenia, and thrombocytopenia were the haematological abnormalities seen in the HIV-positive subjects. HIV viral load correlated with haemoglobin concentration, CD4 count, lymphocyte count, and neutrophil count (p Conclusion: Prognostic factors, such as haemoglobin concentrations, CD4 counts, lymphocyte counts, and neutrophil counts can be used to monitor patients’ viral loads since they correlate with the latter;furthermore, age is a factor that should be considered in the management of HIV-positive patients.

Minimizing the risk of community spread of COVID-19 via institutional quarantine of high-risk travelers with serial viral RNA testing: A successful experience from Macao SAR, China

Macao,a special administrative region(SAR)of the People’s Republic of China,is located in southern China and shares the border with China's Mainland.It is the most densely populated region in the world,with a population of 667400 and a total land area of 32.9 square kilometers in 2019.Since the first case diagnosed on January 22,2020,there was a total of 45 laboratory-confirmed coronavirus disease 2019(COVID-19)cases in Macao,of which 43 patients(96%)were imported cases.To date,all patients had been discharged successfully from Centro Hospitalar Conde de São Januário,a designated hospital to manage all COVID-19 patients in Macao.Eventually,no patient died,and no local community outbreak was noted.This opinion review describes the underlying factors that could have contributed to the successful experience in Macao SAR,China,which include the following:(1)Early implementation of containment measures;(2)Large-scale quarantine using hotel rooms to reduce the risk of a local outbreak;and(3)Multidisciplinary co-operation and transparency of information to the public.Although the successful experience in Macao SAR,China,may not be generalized to other regions,it should not be unreasonable to be well prepared with sufficient logistic support to conduct timely containment and early detection of episodic cases to prevent the backsliding of COVID-19 outbreak.

Turnaround times for molecular testing of pediatric viral cerebrospinal fluid samples in United Kingdom laboratories

BACKGROUND Rapid molecular testing has revolutionized the management of suspected viral meningitis and encephalitis by providing an etiological diagnosis in<90 min with potential to improve outcomes and shorten inpatient stays.However,use of molecular assays can vary widely.AIM To evaluate current practice for molecular testing of pediatric cerebrospinal fluid(CSF)samples across the United Kingdom using a structured questionnaire.METHODS A structured telephone questionnaire survey was conducted between July and August 2020.Data was collected on the availability of viral CSF nucleic acid amplification testing(NAAT),criteria used for testing and turnaround times including the impact of the coronavirus disease 2019 pandemic.RESULTS Of 196/212(92%)microbiology laboratories responded;63/196(32%)were excluded from final analysis as they had no on-site microbiology laboratory and outsourced their samples.Of 133 Laboratories included in the study,47/133(35%)had onsite facilities for viral CSF NAAT.Hospitals currently undertaking onsite NAAT(n=47)had much faster turnaround times with 39 centers(83%)providing results in≤24 h as compared to those referring samples to neighboring laboratories(5/86;6%).CONCLUSION Onsite/near-patient rapid NAAT(including polymerase chain reaction)is recommended wherever possible to optimize patient management in the acute setting.

3'-UTR sequence of Macrobrachium rosenbergii extra small virus(XSV) is important for viral RNA packaging

Dear Editor,The packaging of viral genomic RNA into virus par-ticles is a critical step for virus maturation.This stepincludes the recognition and interaction between the nu-cleocapsid protein and viral RNA.The necessity of viralRNA packaging signals has been described for manyRNA viruses(Cologna R,et al.,2000;Narayanan K,et al.,2001;Tchatalbachev S,et al.,2001).Occasionalpackaging of nongenomic viral RNAs and cellular

RNA pull-down联合质谱分析lncRNA HSFAS在增生性瘢痕中的作用及机制

背景:课题组前期研究发现,增生性瘢痕特异性长链非编码RNA HSFAS是一种可用于增生性瘢痕诊断的新型生物标志物,但其如何在增生性瘢痕中发挥作用尚不清楚。目的:探讨长链非编码RNA HSFAS在增生性瘢痕中的作用及机制。方法:临床收集3例行增生性瘢痕组织切除手术患者的新鲜增生性瘢痕皮肤组织和增生性瘢痕旁正常皮肤组织标本,应用免疫荧光技术检测两种皮肤组织冰冻切片中长链非编码RNA HSFAS的表达。应用酶消化法体外分离增生性瘢痕皮肤组织与正常皮肤组织原代成纤维细胞,采用qRT-PCR检测细胞中长链非编码RNA HSFAS mRNA表达,通过RNA pull-down联合质谱技术检测与长链非编码RNA HSFAS相互结合的蛋白,利用GO和KEGG分析长链非编码RNA HSFAS参与增生性瘢痕进展的主要功能和通路,通过catRAPID和RPISeq网站分析确定长链非编码RNA HSFAS与蛋白的靶向结合。结果与结论:①与正常皮肤组织相比,增生性瘢痕组织中的长链非编码RNA HSFAS表达升高(P<0.05);与正常皮肤组织来源成纤维细胞相比,增生性瘢痕组织来源成纤维细胞中长链非编码RNA HSFAS mRNA表达升高(P<0.05);②RNA pull-down联合质谱技术明确与长链非编码RNA HSFAS相互结合的蛋白有510个;GO和KEGG分析结果显示:这些蛋白主要涉及RNA剪接和加工、染色体合成和分离、细胞周期等过程,其中涉及RNA剪接和加工的蛋白有支架附着因子B2和DICER1,并且与长链非编码RNA HSFAS的结合分数较高;生物信息学技术分析验证结果显示,长链非编码RNA HSFAS与支架附着因子B2和DICER1蛋白存在相互结合;③结果显示,长链非编码RNA HSFAS可能通过与支架附着因子B2和DICER1蛋白相互结合调控RNA剪接和加工修饰影响基因表达,从而促进增生性瘢痕的发生发展。

长链非编码RNA在急性肺损伤中的作用及分子调控机制研究进展

急性肺损伤(ALI)是临床上常见的危重症之一。长链非编码RNA(lncRNA)是一类长度超过200个核苷酸的非蛋白质编码RNA,在染色质形成、转录和转录后翻译等基因表达水平直接或间接参与ALI的发生发展。lncRNA核富集丰富转录物1、lncRNA HOX转录反义基因间RNA及lncRNA牛磺酸上调1等lncRNA可作为竞争性内源RNA,与miR-26a-5p、miR-17-5p及miR-34b-5p等微小RNA结合,调节Wnt1诱导的信号通路蛋白1、Rho关联含卷曲螺旋结合蛋白激酶1蛋白及自噬相关蛋白等下游相关蛋白的表达,参与ALI的发生发展。LncRNA可能通过调控DNA甲基化、组蛋白修饰,在表观遗传水平参与ALI的发生发展;L通过组装转录激活因子和抑制因子,调节白细胞介素6(IL-6)、IL-17、含半胱氨酸的天冬氨酸蛋白水解酶3/9等蛋白质的转录,在转录水平参与ALI的发生发展;与多种RNA结合蛋白相互作用,在转录后水平调控ALI的发生发展。