An epigenetic role for noncoding RNAs and intragenic DNA methylation

A report on the Keystone Symposium 'Epigenetics: Regulation of Chromatin Structure in Development and Disease', Breckenridge, USA, 11-16 April 2007.     

No-nonsense functions for long noncoding RNAs

The mysterious secrets of long noncoding RNAs, often referred to as the Dark Matter of the genome, are gradually coming to light. Several recent papers dig deep to reveal surprisingly complex and diverse functions of these enigmatic molecules.     

Molecular mechanisms of long noncoding RNAs

Long noncoding RNAs (lncRNAs) are an important class of pervasive genes involved in a variety of biological functions. Here we discuss the emerging archetypes of molecular functions that lncRNAs execute-as signals, decoys, guides, and scaffolds. For each archetype, examples from several disparate biological contexts illustrate the commonality of the molecular mechanisms, and these mechanistic views provide useful explanations and predictions of biological outcomes. These archetypes of lncRNA function may be a useful framework to consider how lncRNAs acquire properties as biological signal transducers and hint at their possible origins in evolution. As new lncRNAs are being discovered at a rapid pace, the molecular mechanisms of lncRNAs are likely to be enriched and diversified.     

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。     

Long noncoding RNAs in DNA methylation: new players stepping into the old game

Long non-coding RNAs (lncRNAs) are being discovered as a novel family of regulators of gene expression at the epigenetic level. Emerging lines of evidence demonstrate that interplays between lncRNAs and DNA methylation machinery are an important layer of epigenetic regulation. Here in this mini-review we summarize the current findings in the field and focus particularly on the interactions mediated through direct physical association between lncRNAs and DNA methyltransferases (DNMTs).     

A role of long noncoding RNAs in carcinogenesis

Molecular Biology - The review describes the changes observed in long noncoding RNA (lncRNA) content and function at various stages of carcinogenesis, as well as the prospects of lncRNA application...     

Differential expression of long noncoding RNAs in congenital microtia

ObjectiveTo analyse lncRNA expression profiles in microtia using bioinformatics analysis.MethodsWe examined lncRNA expression profiles in residual ear cartilage and normal ear cartilage from individual congenital microtia patients.ResultsThe gene chips used in this study included 30586 lncRNAs and 26109 mRNA probes. Intotal, 180 lncRNAs with differential expression weredetected in the residual ear cartilage compared with the normal cartilage, including 74 up-regulated and 106down-regulated lncRNAs. Signalling pathway analysis highlighted glyceride metabolism, osteoclast differentiation, andtumour growth. The results of qRT-PCR analysis were consistent with those of themicroarray.ConclusionDifferential expression of lncRNAs occurs in microtia. These lncRNAs and related signalling pathways may play an important role in the occurrence and development ofmicrotia.     

长链非编码RNA的作用机制及其研究方法

长链非编码RNA(Long non-coding RNA, lncRNA)通过多种机制发挥其生物学功能, 这些机制包括基因印记、染色质重塑、细胞周期调控、剪接调控、mRNA降解和翻译调控等。lncRNA通过这些作用机制在不同水平进行基因表达调控。在研究lncRNA功能的过程中, 研究方法的建立和应用起着非常重要的作用。目前用于lncRNA研究的主要方法有：微阵列、转录组测序、Northern印迹、实时荧光定量逆转录-聚合酶链反应、荧光原位杂交、RNA干扰和RNA结合蛋白免疫沉淀等。文章着重介绍了3种前沿方法, 即：在线快速预测RNA与蛋白质相互作用的catRAPID、RNA纯化的染色质分离(Chromatin isolation by RNA purification, ChIRP)以及非编码RNA沉默与定位分析技术(Combined knockdown and localization analysis of non-coding RNAs, c-KLAN)。