哺乳动物中作用于非编码RNA的RNA编辑研究进展

RNA编辑是RNA转录过程中序列变化而引起的一种基因动态调控机制。腺苷脱氨酶（adenosine deaminases acting on RNA, ADAR）参与RNA编辑,将双链RNA中腺苷残基（A）转化为肌苷（I）,接着被转录和拼接成鸟苷（G）。由ADAR催化,作用于RNA的A-I型RNA编辑是人类最常见的转录后修饰。近年来,这种修饰不仅存在于编码RNA中,在非编码RNA（noncoding RNA, ncRNA）中也逐渐被发现,如microRNA（miRNA）、小分子干扰RNA（siRNA）、转运RNA（tRNA）和长链非编码RNA（lncRNA）。这种修饰可能通过对microRNA和mRNA之间结合位点创造或破坏,进而影响ncRNA的生物起源、稳定性和靶向识别功能。目前,对这种生物现象的机制及ADAR底物,尤其是在ncRNA中的特性仍然没有得到充分的认识。主要对哺乳动物中ncRNA上的RNA编辑进行总结,并列举一些阐明其生物学功能的计算方法。     

RNA templating the epigenome

Cellular pathways must be synergized, controlled and organized to manage homeostasis. To achieve high selectivity within the crowded cellular milieu the cell utilizes scaffolding complexes whose role is to bring molecules in proximity thereby controlling and enhancing intermolecular interactions and signaling events. To date, scaffolds have been shown to be composed of proteinaceous units; however, recent evidence has supported the idea that non-coding RNAs may also play a similar role. In this point of view article we discuss recent data on ncRNA scaffolds, with particular focus on ncRNA HOTAIR. Using our current knowledge of signaling networks we discuss the role that RNA may play in writing and regulating histone modifications and the information needed for correct gene expression. Further, we speculate on additional, yet undiscovered roles that ncRNAs may be playing as molecular scaffolds.     

Sequence complementarity between human noncoding RNAs and SARS-CoV-2 genes: What are the implications for human health?

ObjectivesTo investigate in silico the presence of nucleotide sequence complementarity between the RNA genome of Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) and human non-coding (nc)RNA genes.MethodsThe FASTA sequence (NC_045512.2) of each of the 11 SARS-CoV-2 isolate Wuhan-Hu-1 genes was retrieved from NCBI.nlm.nih.gov/gene and the Ensembl.org library interrogated for any base-pair match with human ncRNA genes. SARS-CoV-2 gene-matched human ncRNAs were screened for functional activity using bioinformatic analysis. Finally, associations between identified ncRNAs and human diseases were searched in GWAS databases.ResultsA total of 252 matches were found between the nucleotide sequence of SARS-CoV-2 genes and human ncRNAs. With the exception of two small nuclear RNAs, all of them were long non-coding (lnc)RNAs expressed mainly in testis and central nervous system under physiological conditions. The percentage of alignment ranged from 91.30% to 100% with a mean nucleotide alignment length of 17.5 ± 2.4. Thirty-three (13.09%) of them contained predicted R-loop forming sequences, but none of these intersected the complementary sequences of SARS-CoV-2. However, in 31 cases matches fell on ncRNA regulatory sites, whose adjacent coding genes are mostly involved in cancer, immunological and neurological pathways. Similarly, several polymorphic variants of detected non-coding genes have been associated with neuropsychiatric and proliferative disorders.ConclusionThis pivotal in silico study shows that SARS-CoV-2 genes have Watson-Crick nucleotide complementarity to human ncRNA sequences, potentially disrupting ncRNA epigenetic control of target genes. It remains to be elucidated whether this could result in the development of human disease in the long term.     

Computational RNomics: Structure identification and functional prediction of non-coding RNAs <Emphasis Type="Italic">in silico</Emphasis>

The eukaryotic genome contains varying numbers of non-coding RNA(ncRNA) genes.Computational RNomics takes a multidisciplinary approach,like information science,to resolve the structure and function of ncRNAs.Here,we review the main issues in Computational RNomics of data storage and management,ncRNA gene identification and characterization,ncRNA target identification and functional prediction,and we summarize the main methods and current content of computational RNomics.     

综述: 新型长链非编码RNA(lncRNA)的生物信息学研究进展

非编码RNA (noncoding RNA,ncRNA)是指不被翻译成蛋白质的一类RNA,近几年来关于它们的功能研究越来越引起人们的重视．现在已经发现了一些中小型ncRNA,比如microRNA、snoRNA、tRNA等,但是关于长ncRNA(lncRNA)的研究还不够完善．本篇综述回顾了 ncRNA特别是 lncRNA的生物信息学研究进展,包括它们的研究历程、基本特点、与疾病的关系,以及对已有的预测非编码RNA的计算机方法进行了分析和比较,并且介绍了利用机器学习模型整合新一代高通量测序数据的方法．     

Regulatory non‐coding RNAs in acute myocardial infarction

Acute myocardial infarction (AMI) is one of the most common cardiovascular diseases that leads to high mortality and morbidity globally. Various therapeutic targets for AMI have been investigated in recent years, including the non‐coding RNAs (ncRNAs). NcRNAs, a class of RNA molecules that typically do not code proteins, are divided into several subgroups. Among them, microRNAs (miRNAs) are widely studied for their modulation of several pathological aspects of AMI, including cardiomyocyte apoptosis, inflammation, angiogenesis and fibrosis. It has emerged that long ncRNAs (lncRNAs) and circular RNAs (circRNAs) also regulate these processes via interesting mechanisms. However, the regulatory functions of ncRNAs in AMI and their underlying functional mechanisms have not been systematically described. In this review, we summarize the recent findings involving ncRNA actions in AMI and briefly describe the novel mechanisms of these ncRNAs, highlighting their potential application as therapeutic targets in AMI.     

肠道菌群与非编码RNA互作对疾病影响的研究进展

肠道菌群数量庞大,种类繁多,被认为是一个独立的器官系统,是人体生理和代谢稳态的重要组成部分,肠道菌群的稳态失调以及某些代谢产物的分泌已被证实可以参与人体多种疾病的发生发展。同样,非编码RNA（ncRNA)数量庞大,种类较多,主要包括微小RNA（miRNA)、长链RNA(lncRNA)、环状RNA(circRNA)。ncRNA早期因无蛋白质编码能力未引起重视,随着研究的深入,认识到了其对多种疾病都具有重要的调控作用,近些年获得了更多的关注。目前,多项研究揭示了肠道菌群-ncRNA互作对多种疾病的发生、发展、诊断、治疗等方面的影响,二者互作可能是未来疾病防治的重要突破口。本文就肠道菌群与ncRNA的互作对不同疾病的作用进行综述,以期为疾病的防治提供参考。     

miRNA,lncRNA与心血管疾病

近年来,心血管疾病在我国的发病率和致死率呈逐年上升趋势,已成为威胁我国公众健康的重要疾病之一.尽管长期的研究使人们对心血管疾病有了一定的了解,但是其发病机制尚未完全清楚.非编码RNA(non-coding RNA,ncRNA)是指转录组中不编码蛋白的功能性RNA分子,包括微小RNA(microRNA,miRNA)和长链非编码RNA(long non-coding RNA,lncRNA)等.miRNA是一类在进化上高度保守,具有转录后调节活性的单链非编码小分子RNA.而lncRNA是一类转录本长度超过200个核苷酸的功能性非编码RNA分子.研究表明,这些功能性ncRNA不但在细胞增殖、分化和衰老过程中发挥着重要作用,还参与了癌症、神经退行性疾病和心血管疾病等疾病的病理进程.本文将着重概述miRNA和lncRNA在心血管疾病中的作用及其最新研究进展.     

Expression profiling of microRNA using oligo DNA arrays

After 12 years from its first application, microarray technology has become the reference technique to monitor gene expression of thousands of genes in the same experiment. In the past few years an increasing amount of evidence showed the importance of non-coding RNA (ncRNA) in different human diseases. The microRNAs (miRNAs) are one of the groups of ncRNA. They are small RNA fragments, 19-25 nucleotides long, with a main regulatory function on both protein coding genes and non-coding RNAs. The application of microarray platforms applied to miRNA profiling determined their deregulation in virtually all human diseases that have been studied. We previously developed a custom miRNA microarray platform, and here we describe the protocol we used to work with it including the oligo design strategy, the microarray printing protocol, the target-probe hybridization and the signal detection.     

MicroRNA，lncRNA与神经退行性疾病

综述了microRNA和lncRNA在一些神经退行性疾病病理生理中的作用机制．随着社会生产的发展,人类文明的进步,人口日益老年化,神经退行性疾病正在全球范围内流行,严重地危害着人类的健康．尽管长期的研究使人们对神经退行性疾病有了比较全面和深入的了解,但是其背后隐藏的发病机制仍然是个谜．人类基因组约98%的转录产物为非编码RNA(ncRNA),在生命活动中有着许多鲜为人知的广泛而多样性的生物功能．小分子RNA(microRNA)是研究得相对比较深入的一类小ncRNA,最近2～3年,长非编码RNA(lncRNA)受到人们的重视,已积累了一些相关研究成果．