长链非编码RNA生物学功能及其意义研究进展

人类基因组DNA核苷酸序列中约93%能被转录为RNA,其中仅2%的转录产物被翻译为蛋白质,余下98%属于非编码RNA（non-coding RNA,ncRNA）。ncRNA中长度超过200 nt的称为长链非编码RNA（long non-coding RNA,LncRNA）,长期以来LncRNA被认为是转录过程中的副产物而不具有生物学功能。近年随着微小RNA（microRNA,miRNA）的研究进展,揭示了ncRNA在人类基因转录后调节、细胞生长、分化、增殖中起着相当重要的作用。同时也提示,相比miRNA,在细胞内转录比例更高的LncRNA具有极其复杂而重要的生物学功能,并与人类疾病密切相关。结合LncRNA的表观遗传学功能及其病理生理意义作一简述。     

ADAR1介导的RNA编辑在血液肿瘤中的调控作用

RNA编辑是发生于双链RNA（dsRNA）上的一类重要转录后反应,可通过碱基插入、缺失或替换的方式改变RNA的核苷酸序列从而丰富转录组和蛋白质组水平的多样性。哺乳动物中最常见的RNA编辑是ADAR家族介导的腺嘌呤-次黄嘌呤编辑（A-to-I）,其在碱基配对过程中被识别为鸟嘌呤。人类转录组中已报道了数百万个A-to-I编辑位点,而ADAR1是最主要的催化酶。在血液肿瘤中,ADAR1的失调将直接影响基因编码区、非编码区和miRNA前体的A-to-I编辑状态,从而导致一系列分子事件改变,如蛋白质编码序列改变、内含子滞留、选择性剪接和miRNA生物发生受抑制。近年来研究发现,异常的RNA编辑导致分子调控网络的紊乱,促进细胞增殖、凋亡受阻和细胞耐药,是白血病干细胞（LSCs）生成和干性维持的重要因素。目前,以RNA编辑为靶点的新药（如rebecsinib）已经在动物实验中取得良好疗效。有别于传统抗肿瘤药,表观遗传抗肿瘤药有望克服血液肿瘤的耐药、复发难题,为患者提供全新治疗选择。本综述总结了ADAR1介导的RNA编辑在血液肿瘤中的作用机制及其生物学功能研究的进展,并探讨了其在药物研发和临床应用中的价值。     

长非编码RNA

人类基因组序列的约5%～10%被稳定转录,蛋白质编码基因仅约占1%,其余4%～9%的序列虽能转录,但转录物功能尚不明确。尽管如此,已确证在非蛋白质编码转录物中,含有具备调节功能的非编码RNA(noncoding RNA,ncRNA)。与具有调节功能的短链非编码RNA[如微RNA(microRNA)、小干扰RNA(siRNA),、Piwi-RNA]相比,长非编码RNA(long noncoding RNA,lncRNA)在数量上占大多数。lncRNA通过多种方式产生,以多种途径调节靶基因表达,参与调控生物体生长、发育、衰老、死亡等过程;lncRNA功能异常往往导致疾病发生。本文综述了lncRNA的起源、分类、作用分子机制及lncRNA异常与疾病的相关性等内容,旨在充分了解这一重要新型调控分子。     

非编码RNA参与调控哮喘T细胞功能的研究进展

支气管哮喘(简称哮喘)是一种以气道炎性反应、高反应性及气道重塑为特征的慢性炎症性疾病,T细胞在其中发挥着至关重要的作用。非编码RNA (non-coding RNA, ncRNA)是转录组中不编码蛋白质的RNA分子,主要包括微小RNA (microRNA,miRNA)、长链非编码RNA (long non-coding RNA, lncRNA)、环状RNA (circular RNA, circRNA)等,广泛存在于真核生物基因组中,参与调控多种生物学过程。已有研究表明,ncRNA在哮喘T细胞的活化及转换等过程中起着重要作用,其具体作用机制及临床应用值得深入探讨。本文综合分析了近年来miRNA、lncRNA和circRNA在哮喘T细胞功能调控中的研究进展,为更好地理解哮喘发病机制和提高诊断水平提供新思路,同时也为利用ncRNA的调节潜能开发治疗策略提供理论依据。     

植物非编码RNA的研究进展

非编码RNA(non-coding RNA, ncRNA)是一类广泛存在于多种生物体中,缺乏明确的开放阅读框,不编码蛋白质的RNA分子.目前已从部分植物中分离到一些ncRNA,它们直接以RNA分子的形式在植物体内发挥重要的调节功能,影响细胞分化和个体发育、基因转录调控、mRNA稳定性、RNA加工与修饰、信号传导、以及环境适应调节等.植物ncRNA的研究为深入了解植物的生长发育及系统进化提供了重要信息.     

腺苷酸脱氨酶介导的 RNA 编辑在神经系统疾病中的作用

在哺乳动物中枢神经系统中最常见的RNA编辑是由ADAR(腺苷酸脱氨酶)所介导的从腺苷酸(adnosine,A)到肌苷酸(inosine,I)的转录后修饰过程。许多研究表明RNA编辑对于维持中枢神经系统的稳态和动物正常的生理功能必不可少。因此,RNA编辑可能是神经发育、神经系统功能以及神经系统疾病之间关键性的联系。本综述旨在对目前ADAR介导的RNA编辑在中枢神经系统疾病中作用机制的相关研究加以归纳。     

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．     

植物中的非编码RNA及其作用机制

非编码RNA(non-codingRNA,ncRNA)是近年来发现的一类能够转录但不能编码蛋白质、具有特定功能的RNA分子。ncRNA参与了生命过程中的许多重要环节。该文主要介绍植物中的非编码RNA的类型、研究方法以及功能。     

长链内含子非编码RNA在基因表达过程中的调控作用

在绝大多数人类基因中都存有非蛋白编码RNA（non-coding RNA,ncRNA）.长链内含子ncRNA（long intronic non-coding RNA,lincRNA）是众多ncRNA中的一员,而内含子区域则是具有调节性的ncRNA的关键源.长链内含子ncRNA可通过作为短链RNA的前体、或是与启动子元件的交互作用、组蛋白甲基化修饰、蛋白编码RNA选择性剪接以及蛋白质编码RNA的稳定性,从而对基因表达进行调控.至此我们可以逐步揭示出基于长链内含子ncRNA的调控系统模式.     

长链非编码RNA的研究现状

长链非编码RNA（lncRNA）是一类长度大于200bp的非编码RNA,无蛋白质编码功能,物种间保守性差,具有较强的组织特异性和时空特异性。研究表明ncRNA具有广泛的生物学功能,如参与RNA的生成与加工、转录调控、染色质重塑等,且作用机制复杂,如能通过绑定特点蛋白质参与转录调节或作为ceRNA参与转录后调控。但lncRNA的结构复杂,功能研究进展缓慢,目前仍难以对其细致分类。从基本特征、分类、功能、数据库、研究工具及其与癌症之间的关系等方面对lncRNA的研究进展进行综述,以期为lncRNA后续研究提供参考。     

ADAR-mediated RNA editing in non-coding RNA sequences

Adenosine to inosine (A-to-I) RNA editing is the most abundant editing event in animals. It converts adenosine to inosine in double-stranded RNA regions through the action of the adenosine deaminase acting on RNA (ADAR) proteins. Editing of pre-mRNA coding regions can alter the protein codon and increase functional diversity. However, most of the A-to-I editing sites occur in the non-coding regions of pre-mRNA or mRNA and non-coding RNAs. Untranslated regions (UTRs) and introns are located in pre-mRNA non-coding regions, thus A-to-I editing can influence gene expression by nuclear retention, degradation, alternative splicing, and translation regulation. Non-coding RNAs such as microRNA (miRNA), small interfering RNA (siRNA) and long non-coding RNA (lncRNA) are related to pre-mRNA splicing, translation, and gene regulation. A-to-I editing could therefore affect the stability, biogenesis, and target recognition of non-coding RNAs. Finally, it may influence the function of non-coding RNAs, resulting in regulation of gene expression. This review focuses on the function of ADAR-mediated RNA editing on mRNA non-coding regions (UTRs and introns) and non-coding RNAs (miRNA, siRNA, and lncRNA).     

Stress-induced apoptosis associated with null mutation of ADAR1 RNA editing deaminase gene

One type of RNA editing involves the conversion of adenosine residues into inosine in double-stranded RNA through the action of adenosine deaminases acting on RNA (ADAR). A-to-I RNA editing of the coding sequence could result in synthesis of proteins not directly encoded in the genome. ADAR edits also non-coding sequences of target RNAs, such as introns and 3'-untranslated regions, which may affect splicing, translation, and mRNA stability. Three mammalian ADAR gene family members (ADAR1-3) have been identified. Here we investigated phenotypes of mice homozygous for ADAR1 null mutation. Although live ADAR1-/- embryos with normal gross appearance could be recovered up to E11.5, widespread apoptosis was detected in many tissues. Fibroblasts derived from ADAR1-/- embryos were also prone to apoptosis induced by serum deprivation. Our results demonstrate an essential requirement for ADAR1 in embryogenesis and suggest that it functions to promote survival of numerous tissues by editing one or more double-stranded RNAs required for protection against stress-induced apoptosis.     

Modulation of microRNA processing and expression through RNA editing by ADAR deaminases

Adenosine deaminases acting on RNA (ADARs) are involved in editing of adenosine residues to inosine in double-stranded RNA (dsRNA). Although this editing recodes and alters functions of several mammalian genes, its most common targets are noncoding repeat sequences, indicating the involvement of this editing system in currently unknown functions other than recoding of protein sequences. Here we show that specific adenosine residues of certain microRNA (miRNA) precursors are edited by ADAR1 and ADAR2. Editing of pri-miR-142, the precursor of miRNA-142, expressed in hematopoietic tissues, resulted in suppression of its processing by Drosha. The edited pri-miR-142 was degraded by Tudor-SN, a component of RISC and also a ribonuclease specific to inosine-containing dsRNAs. Consequently, mature miRNA-142 expression levels increased substantially in ADAR1 null or ADAR2 null mice. Our results demonstrate a new function of RNA editing in the control of miRNA biogenesis.     

Editing independent effects of ADARs on the miRNA/siRNA pathways

Adenosine deaminases acting on RNA (ADARs) are best known for altering the coding sequences of mRNA through RNA editing, as in the GluR‐B Q/R site. ADARs have also been shown to affect RNA interference (RNAi) and microRNA processing by deamination of specific adenosines to inosine. Here, we show that ADAR proteins can affect RNA processing independently of their enzymatic activity. We show that ADAR2 can modulate the processing of mir‐376a2 independently of catalytic RNA editing activity. In addition, in a Drosophila assay for RNAi deaminase‐inactive ADAR1 inhibits RNAi through the siRNA pathway. These results imply that ADAR1 and ADAR2 have biological functions as RNA‐binding proteins that extend beyond editing per se and that even genomically encoded ADARs that are catalytically inactive may have such functions.     

Elucidating the inosinome: global approaches to adenosine-to-inosine RNA editing

Catalysed by members of the adenosine deaminase acting on RNA (ADAR) family of enzymes, adenosine-to-inosine (A-to-I) editing converts adenosines in RNA molecules to inosines, which are functionally equivalent to guanosines. Recently, global approaches to studying this widely conserved phenomenon have emerged. The use of bioinformatics, high-throughput sequencing and other approaches has increased the number of known editing sites by several orders of magnitude, and we now have a greater understanding of the control and the biological significance of editing. This Progress article reviews some of these recent global studies and their results.