Transcription regulation by long non-coding RNAs: mechanisms and disease relevance

IF 81.3 1区 生物学 Q1 CELL BIOLOGY
Jorge Ferrer, Nadya Dimitrova
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Abstract

Long non-coding RNAs (lncRNAs) outnumber protein-coding transcripts, but their functions remain largely unknown. In this Review, we discuss the emerging roles of lncRNAs in the control of gene transcription. Some of the best characterized lncRNAs have essential transcription cis-regulatory functions that cannot be easily accomplished by DNA-interacting transcription factors, such as XIST, which controls X-chromosome inactivation, or imprinted lncRNAs that direct allele-specific repression. A growing number of lncRNA transcription units, including CHASERR, PVT1 and HASTER (also known as HNF1A-AS1) act as transcription-stabilizing elements that fine-tune the activity of dosage-sensitive genes that encode transcription factors. Genetic experiments have shown that defects in such transcription stabilizers often cause severe phenotypes. Other lncRNAs, such as lincRNA-p21 (also known as Trp53cor1) and Maenli (Gm29348) contribute to local activation of gene transcription, whereas distinct lncRNAs influence gene transcription in trans. We discuss findings of lncRNAs that elicit a function through either activation of their transcription, transcript elongation and processing or the lncRNA molecule itself. We also discuss emerging evidence of lncRNA involvement in human diseases, and their potential as therapeutic targets. This Review discusses the emerging roles of long non-coding RNAs (lncRNAs) in the regulation of transcription, for example by controlling the expression of transcription factors. Some lncRNA loci function in trans, but most function in cis, through their own transcription or through the lncRNA transcripts themselves.

Abstract Image

Abstract Image

长非编码 RNA 的转录调控:机制与疾病相关性
长非编码 RNA(lncRNA)的数量超过了蛋白质编码转录本,但它们的功能在很大程度上仍不为人所知。在这篇综述中,我们将讨论 lncRNA 在基因转录控制中的新作用。一些特征最明显的 lncRNAs 具有重要的转录顺式调控功能,而 DNA 相互作用转录因子无法轻松实现这些功能,如控制 X 染色体失活的 XIST 或指导等位基因特异性抑制的印记 lncRNAs。越来越多的lncRNA转录单元,包括CHASERR、PVT1和HASTER(又称HNF1A-AS1)作为转录稳定元件,对编码转录因子的剂量敏感基因的活性进行微调。遗传实验表明,这类转录稳定因子的缺陷往往会导致严重的表型。其他lncRNA,如lincRNA-p21(又称Trp53cor1)和Maenli(Gm29348)有助于基因转录的局部激活,而不同的lncRNA则影响基因的反式转录。我们讨论了通过激活其转录、转录本伸长和加工或 lncRNA 分子本身激发功能的 lncRNA 的研究结果。我们还讨论了lncRNA参与人类疾病的新证据,以及它们作为治疗靶点的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Nature Reviews Molecular Cell Biology
Nature Reviews Molecular Cell Biology 生物-细胞生物学
CiteScore
173.60
自引率
0.50%
发文量
118
审稿时长
6-12 weeks
期刊介绍: Nature Reviews Molecular Cell Biology is a prestigious journal that aims to be the primary source of reviews and commentaries for the scientific communities it serves. The journal strives to publish articles that are authoritative, accessible, and enriched with easily understandable figures, tables, and other display items. The goal is to provide an unparalleled service to authors, referees, and readers, and the journal works diligently to maximize the usefulness and impact of each article. Nature Reviews Molecular Cell Biology publishes a variety of article types, including Reviews, Perspectives, Comments, and Research Highlights, all of which are relevant to molecular and cell biologists. The journal's broad scope ensures that the articles it publishes reach the widest possible audience.
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