长链非编码RNA与表观遗传调控

近年来,表观遗传学(epigenetics)备受关注.表观遗传调控的方式主要包括DNA甲基化、组蛋白修饰和染色质重塑等.ENCODE计划及随后的研究发现,人类基因组中仅有很小一部分DNA序列负责编码蛋白质,而其余大部分被转录为非编码RNA(non-codingRNA,ncRNA).其中长链非编码RNA(long non-codingRNA,lncRNA)是一类长度大于200nt并且缺乏蛋白质编码能力的RNA分子.越来越多的研究表明,lncRNAs能够通过表观遗传调控、转录调控以及转录后调控等多个层面调节基因的表达,从而参与细胞增殖、分化和凋亡等多种生物学过程.本文将着重综述lncRNAs在表观遗传调控中的作用及其最新的研究进展.     

Long non-coding RNAs and their implications in cancer epigenetics

LncRNAs (long non-coding RNAs) have emerged as key molecular players in the regulation of gene expression in different biological processes. Their involvement in epigenetic processes includes the recruitment of histone-modifying enzymes and DNA methyltransferases, leading to the establishment of chromatin conformation patterns that ultimately result in the fine control of genes. Some of these genes are related to tumorigenesis and it is well documented that the misregulation of epigenetic marks leads to cancer. In this review, we highlight how some of the lncRNAs implicated in cancer are involved in the epigenetic control of gene expression. While very few lncRNAs have already been identified as players in determining the cancer-survival outcome in a number of different cancer types, for most of the lncRNAs associated with epigenetic regulation only their altered pattern of expression in cancer is demonstrated. Thanks to their tissue-specificity features, lncRNAs have already been proposed as diagnostic markers in specific cancer types. We envision the discovery of a wealth of novel spliced and unspliced intronic lncRNAs involved in epigenetic networks or in highly location-specific epigenetic control, which might be predominantly altered in specific cancer subtypes. We expect that the characterization of new lncRNA (long non-coding RNA)–protein and lncRNA–DNA interactions will contribute to the discovery of potential lncRNA targets for use in therapies against cancer.     

LncRNA调控骨骼肌发育的分子机制及其在家养动物中的研究进展

骨骼肌是维持机体功能必不可少的组织,与家养动物的产肉率等重要经济性状密切相关。近年来,高通量测序鉴定了大量与骨骼肌生成相关的长链非编码RNA (long non-coding RNA, lncRNA),它们可作为调节因子在表观调控、转录调控以及转录后调控等多个层面调控基因表达。lncRNA通过靶向关键因子参与调控骨骼肌发育的各个环节,包括骨骼肌干细胞增殖、迁移、分化,成肌细胞增殖、分化、肌管融合,肌纤维肥大和纤维类型转换等过程。本文重点归纳了lncRNA在人和小鼠骨骼肌发育中的分子调控机制,介绍了lncRNA的研究方法,综述了lncRNA在家养动物骨骼肌发育中的研究进展,分析了目前家养动物lncRNA研究所面临的困难和挑战,最后展望了未来家养动物lncRNA研究的方向,以期为进一步阐明骨骼肌生长发育的分子调控机制提供参考。     

基因组印记中的长非编码RNA

长非编码RNA(lnc RNA)是长度大于200 bp的一类非编码蛋白的RNA,因其在基因组中含量巨大以及重要的生物学功能引起了学术界的广泛关注.基因组印记是一种表观遗传现象,lnc RNAs通过建立靶基因的印记而发挥重要的生物功能.基因组印记可以用来研究lnc RNAs在转录和转录后水平调控基因表达的分子机制.本文选取6个印记机制研究比较透彻的印记区域,包括Kcnq1/Cdkn1c、Igf2r/Airn、Prader-Willi(PWS)/Angelman(AS)、Snurf/Snrpn、Dlk1-Dio3和H19/Igf2.通过介绍包括基因间lnc RNAs(H19、Ipw和Meg3)、反义lnc RNAs(Kcnq1ot1、Airn、Ube3a-ATS)和增强子lnc RNAs(IG-DMR e RNAs)在内的3种类型lnc RNAs在印记调控中的作用,从而了解lnc RNAs通过顺式或(/和)反式作用多种机制调控亲本特异性靶基因的表达.了解印记基因簇中lnc RNAs的作用方式将有助于我们揭示lnc RNAs在整个基因组中的作用机制.     

DNA methylation and gene expression profiles characterize epigenetic regulation of lncRNAs in colon adenocarcinoma

The long noncoding RNAs (lncRNAs) are associated with tumorigenesis and progression of cancer. While DNA methylation is a common epigenetic regulator of gene expression, the methylation of lncRNAs was rarely studied. To address this gap, we integrated DNA methylation and RNA-seq data to characterize the landscape of lncRNA methylation in colon adenocarcinoma (COAD). We collected and analyzed the lncRNA expression and methylation data from The Cancer Genome Atlas and Cancer Cell Line Encyclopedia to identify the epigenetically regulated lncRNAs. We further investigated the biological and clinical relevance of the identified lncRNAs via bioinformatics analysis. We identified 20 epigenetically upregulated lncRNAs in COAD, including several well-studied lncRNAs whose methylation regulation were poorly investigated, such as PVT1 and UCA1. We also revealed several novel tumor-associated lncRNAs in COAD, including GATA2-As1 and CYTOR. Next, we explored their biology function using gene set enrichment analysis and competitive endogenous RNA analysis. We characterized the methylation landscape of lncRNA in COAD and identified 20 epigenetically upregulated lncRNAs. Our findings will shed new light on the epigenetic regulation of lncRNA expression by DNA methylation.     

长链非编码RNA数据库资源

长链非编码RNA（long non coding RNA, lncRNA)在多个水平参与调节机体的各项基础生物进程,其功能紊乱常伴随疾病的发生。鉴定lncRNA的生物学功能已成为近年来的研究热点。然而,目前从各种真核生物高通量测序中鉴定的几十万个lncRNA中,只有极少数的功能已被实验验证,这对于该领域的深入研究是个巨大的挑战。因此,许多科研机构都建立了lncRNA数据库,并且持续周期性更新,这为研究者共享、注释和分析lncRNA功能提供了十分有效的工具。本文从lncRNA原始资源整合、筛选、鉴定及功能分析和lncRNA与人类疾病等4个方面介绍各lncRNA数据库资源的最新特征和应用范围。这为研究者在选择不同数据库资源进行lncRNA鉴定和分析时提供参考。     

Epigenetics in C. elegans: facts and challenges

Epigenetics is defined as the study of heritable changes in gene expression that are not accompanied by changes in the DNA sequence. Epigenetic mechanisms include histone post-translational modifications, histone variant incorporation, non-coding RNAs, and nucleosome remodeling and exchange. In addition, the functional compartmentalization of the nucleus also contributes to epigenetic regulation of gene expression. Studies on the molecular mechanisms underlying epigenetic phenomena and their biological function have relied on various model systems, including yeast, plants, flies, and cultured mammalian cells. Here we will expose the reader to the current understanding of epigenetic regulation in the roundworm C. elegans. We will review recent models of nuclear organization and its impact on gene expression, the biological role of enzymes modifying core histones, and the function of chromatin-associated factors, with special emphasis on Polycomb (PcG) and Trithorax (Trx-G) group proteins. We will discuss how the C. elegans model has provided novel insight into mechanisms of epigenetic regulation as well as suggest directions for future research.     

调控肌肉生长发育的lncRNAs

长链非编码RNA（long non-coding RNA, lncRNA）是存在于真核生物体内的一种长度大于200 nt主要由RNA聚合酶Ⅱ转录而来的RNAs,且不具有编码蛋白质能力。作为机体基因调控网络的重要调节因子,lncRNA在X染色体沉默、脂肪代谢、细胞生长发育等方面发挥重要作用。近期研究结果表明,lncRNA通过介导表观遗传、转录水平和转录后水平调控等方式,参与骨骼肌的生长发育以及分化过程的调节,包括调控肌源性干细胞和成肌细胞的增殖、分化和肌管的融合等进程,从而影响肌肉的生长发育。本文概述了lncRNA的分类与生物学功能,归纳了lncRNA的作用机制,重点介绍参与骨骼肌生长发育调控的lncRNAs,分析目前lncRNA研究面临的机遇及挑战,展望未来研究的热点与方向,以期为lncRNA在肌肉生长调控方面开展深入研究提供参考。     

Long non-coding RNAs and chromatin modifiers

The emergence of long non-coding RNAs (lncRNAs) has shaken up our conception of gene expression regulation, as lncRNAs take prominent positions as components of cellular networks. Several cellular processes involve lncRNAs, and a significant number of them have been shown to function in cooperation with chromatin modifying enzymes to promote epigenetic activation or silencing of gene expression. Different model mechanisms have been proposed to explain how lncRNAs achieve regulation of gene expression by interacting with the epigenetic machinery. Here we describe these models in light of the current knowledge of lncRNAs, such as Xist and HOTAIR, and discuss recent literature on the role of the three-dimensional structure of the genome in the mechanism of action of lncRNAs and chromatin modifiers.     

Genome‐wide characterization and developmental expression profiling of long non‐coding RNAs in Sogatella furcifera

The genome‐wide characterization of long non‐coding RNA (lncRNA) in insects demonstrates their importance in fundamental biological processes. Essentially, an in‐depth understanding of the functional repertoire of lncRNA in insects is pivotal to insect resources utilization and sustainable pest control. Using a custom bioinformatics pipeline, we identified 1861 lncRNAs encoded by 1852 loci in the Sogatella furcifera genome. We profiled lncRNA expression in different developmental stages and observed that the expression of lncRNAs is more highly temporally restricted compared to protein‐coding genes. More up‐regulated Sogatella furcifera lncRNA expressed in the embryo, 4th and 5th instars, suggesting that increased lncRNA levels may play a role in these developmental stages. We compared the relationship between the expression of Sogatella furcifera lncRNA and its nearest protein gene and found that lncRNAs were more correlated to their downstream coding neighbors on the opposite strand. Our genome‐wide profiling of lncRNAs in Sogatella furcifera identifies exciting candidates for characterization of lncRNAs, and also provides information on lncRNA regulation during insect development.