The p53-induced lincRNA-p21 derails somatic cell reprogramming by sustaining H3K9me3 and CpG methylation at pluripotency gene promoters

Recent studies have boosted our understanding of long noncoding RNAs (lncRNAs) in numerous biological processes, but few have examined their roles in somatic cell reprogramming. Through expression profiling and functional screening, we have identified that the large intergenic noncoding RNA p21 (lincRNA-p21) impairs reprogramming. Notably, lincRNA-p21 is induced by p53 but does not promote apoptosis or cell senescence in reprogramming. Instead, lincRNA-p21 associates with the H3K9 methyltransferase SETDB1 and the maintenance DNA methyltransferase DNMT1, which is facilitated by the RNA-binding protein HNRNPK. Consequently, lincRNA-p21 prevents reprogramming by sustaining H3K9me3 and/or CpG methylation at pluripotency gene promoters. Our results provide insight into the role of lncRNAs in reprogramming and establish a novel link between p53 and heterochromatin regulation.     

长链非编码RNA作为潜在药物靶点的研究进展

随着生命科学的不断发展,2012年DNA元件百科全书（ENCODE）项目进一步丰富了人类基因组功能元件的相关信息。该项目 发现人类基因组超过80%的序列会被转录,其中大部分转录本是非编码RNA（ncRNA）。目前,在这些非编码RNA中,小RNA的研究 相对深入,而长链非编码RNA（lncRNA）的研究相对较少。越来越多研究表明,很多lncRNA参与到人类重大疾病的发生、发展过程之 中,并且一些动物实验证实lncRNA可作为药物靶点。因此,从lncRNA角度筛选新的药物靶点也越来越受到研究者的关注。重点总结了 lncRNA的生物学功能及作为潜在药物靶点的研究进展。     

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.     

线粒体LncRNA

长链非编码RNA（long noncoding RNAs,lncRNAs）是一类长度大于200个核苷酸的非蛋白质编码RNA。绝大多数lncRNA来源于核基因组。但近年研究发现,一些lncRNA是由线粒体基因组编码、转录而成,或定位于线粒体。本文将从线粒体lncRNA的发现与主要种类、线粒体lncRNA的加工和结构,以及它们的功能和应用等几个方面,对线粒体lncRNA进行阐述。线粒体lncRNA可能成为心血管疾病或肿瘤诊断的生物标志物,或在调控线粒体基因表达等方面发挥重要功能。     

Identifying sequence features that drive ribosomal association for lncRNA

Background

With the increasing number of annotated long noncoding RNAs (lncRNAs) from the genome, researchers are continually updating their understanding of lncRNAs. Recently, thousands of lncRNAs have been reported to be associated with ribosomes in mammals. However, their biological functions or mechanisms are still unclear.

Results

In this study, we tried to investigate the sequence features involved in the ribosomal association of lncRNA. We have extracted ninety-nine sequence features corresponding to different biological mechanisms (i.e., RNA splicing, putative ORF, k-mer frequency, RNA modification, RNA secondary structure, and repeat element). An \(\mathcal {L}1\)-regularized logistic regression model was applied to screen these features. Finally, we obtained fifteen and nine important features for the ribosomal association of human and mouse lncRNAs, respectively.

Conclusion

To our knowledge, this is the first study to characterize ribosome-associated lncRNAs and ribosome-free lncRNAs from the perspective of sequence features. These sequence features that were identified in this study may shed light on the biological mechanism of the ribosomal association and provide important clues for functional analysis of lncRNAs.

     

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.     

The long noncoding RNA Vax2os1 controls the cell cycle progression of photoreceptor progenitors in the mouse retina

Long noncoding RNAs (lncRNAs) are emerging as regulators of many basic cellular pathways. Several lncRNAs are selectively expressed in the developing retina, although little is known about their functional role in this tissue. Vax2os1 is a retina-specific lncRNA whose expression is restricted to the mouse ventral retina. Here we demonstrate that spatiotemporal misexpression of Vax2os1 determines cell cycle alterations in photoreceptor progenitor cells. In particular, the overexpression of Vax2os1 in the developing early postnatal mouse retina causes an impaired cell cycle progression of photoreceptor progenitors toward their final committed fate and a consequent delay of their differentiation processes. At later developmental stages, this perturbation is accompanied by an increase of apoptotic events in the photoreceptor cell layer, in comparison with control retinas, without affecting the proper cell layering in the adult retina. Similar results are observed in mouse photoreceptor-derived 661W cells in which Vax2os1 overexpression results in an impairment of the cell cycle progression rate and cell differentiation. Based on these results, we conclude that Vax2os1 is involved in the control of cell cycle progression of photoreceptor progenitor cells in the ventral retina. Therefore, we propose Vax2os1 as the first example of lncRNA that acts as a cell cycle regulator in the mammalian retina during development.     

Strategies to identify long noncoding RNAs involved in gene regulation

Long noncoding RNAs (lncRNAs) have been detected in nearly every cell type and found to be fundamentally involved in many biological processes. The characterization of lncRNAs has immense potential to advance our comprehensive understanding of cellular processes and gene regulation, along with implications for the treatment of human disease. The recent ENCODE (Encyclopedia of DNA Elements) study reported 9,640 lncRNA loci in the human genome, which corresponds to around half the number of protein-coding genes. Because of this sheer number and their functional diversity, it is crucial to identify a pool of potentially relevant lncRNAs early on in a given study. In this review, we evaluate the methods for isolating lncRNAs by immunoprecipitation and review the advantages, disadvantages, and applications of three widely used approaches ?C microarray, tiling array, and RNA-seq ?C for identifying lncRNAs involved in gene regulation. We also look at ways in which data from publicly available databases such as ENCODE can support the study of lncRNAs.