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长非编码 RNA:从生物学特征和功能到疾病的洞察。

Long Noncoding RNAs: Insights from Biological Features and Functions to Diseases.

机构信息

Department of Molecular Biology, Institute of Basic Medicine, School of Life Sciences, Chinese PLA General Hospital, Beijing, 100853, China.

出版信息

Med Res Rev. 2013 May;33(3):517-53. doi: 10.1002/med.21254. Epub 2012 Feb 8.

Abstract

Over the past decade, genome-wide transcriptomic studies have shown that the mammalian genome is pervasively transcribed and produces many thousands of transcriptomes without bias from previous genome annotations. This finding, together with the discovery of a plethora of unexpected RNAs that have no obvious coding capacities, have challenged the traditional views that proteins are the main protagonists of cellular functions and that RNA is merely an intermediary between DNA sequence and its encoded protein. There are many different kinds of products that are generated by this pervasive transcription; this review focuses on long noncoding RNAs (lncRNAs) that have shown spatial and temporal specific patterns of expression and regulation in a wide variety of cells and tissues, adding significant complexity to the understanding of their biological roles. Recent research has shed new light onto the biological function significance of lncRNAs. Here, we review the rapidly advancing field of lncRNAs, describing their biological features and their roles in regulation of gene expression. Moreover, we highlight some recent advances in our understanding of ncRNA-mediated regulation of stem cell pluripotency, morphogenesis, and development, focusing mainly on the regulatory roles of lncRNAs. Finally, we consider the potential medical implications, and the potential use of lncRNAs in drug development and discovery and in the identification of molecular markers of diseases, including cancer.

摘要

在过去的十年中,全基因组转录组研究表明,哺乳动物基因组广泛转录,并产生了数千种转录本,而不受先前基因组注释的偏见。这一发现,加上大量意想不到的 RNA 的发现,这些 RNA 没有明显的编码能力,挑战了蛋白质是细胞功能的主要主角,而 RNA 仅仅是 DNA 序列与其编码的蛋白质之间的中介的传统观点。这种广泛转录产生了许多不同种类的产物;本综述重点介绍了长非编码 RNA(lncRNA),它们在广泛的细胞和组织中表现出空间和时间特异性的表达和调控模式,为理解它们的生物学功能增加了显著的复杂性。最近的研究为 lncRNA 的生物学功能意义提供了新的线索。在这里,我们回顾了 lncRNA 领域的快速发展,描述了它们的生物学特征及其在基因表达调控中的作用。此外,我们强调了一些关于 ncRNA 介导的干细胞多能性、形态发生和发育调控的最新进展,主要关注 lncRNA 的调控作用。最后,我们考虑了潜在的医学意义,以及 lncRNA 在药物开发和发现以及疾病分子标志物(包括癌症)鉴定中的潜在用途。

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