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通过非编码RNA介导的表观遗传变化实现转录基因沉默。

Transcriptional gene silencing through epigenetic changes mediated by non-coding RNAs.

作者信息

Malecová Barbora, Morris Kevin V

机构信息

The Scripps Research Institute, Department of Molecular and Experimental Medicine, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

出版信息

Curr Opin Mol Ther. 2010 Apr;12(2):214-22.

Abstract

Chromatin remodeling guided by non-coding RNA (ncRNA) contributes mechanistically to the establishment of chromatin structure and to the maintenance of epigenetic memory. Various ncRNAs have been identified as regulators of chromatin structure and gene expression. The widespread occurrence of antisense transcription in eukaryotes emphasizes the prevalence of gene regulation by natural antisense transcripts. Recently, antisense ncRNAs have been implicated in the silencing of tumor suppressor genes through epigenetic remodeling events. Characterization of the antisense RNAs involved in the development or maintenance of oncogenic states may define ncRNAs as early biomarkers for the emergence of cancer, and could have a significant impact on the development of tools for disease diagnosis and treatment. In this review, current knowledge on the mechanisms of ncRNA-mediated transcriptional gene silencing in humans is discussed, and parallels between the establishment of a silent chromatin state mediated by siRNAs and long antisense ncRNAs are highlighted.

摘要

由非编码RNA(ncRNA)引导的染色质重塑在机制上有助于染色质结构的建立和表观遗传记忆的维持。各种ncRNA已被鉴定为染色质结构和基因表达的调节因子。真核生物中反义转录的广泛存在强调了天然反义转录本对基因调控的普遍性。最近,反义ncRNA通过表观遗传重塑事件参与了肿瘤抑制基因的沉默。对参与致癌状态发展或维持的反义RNA的表征可能将ncRNA定义为癌症出现的早期生物标志物,并可能对疾病诊断和治疗工具的开发产生重大影响。在这篇综述中,我们讨论了目前关于人类中ncRNA介导的转录基因沉默机制的知识,并强调了由小干扰RNA(siRNA)和长反义ncRNA介导的沉默染色质状态建立之间的相似之处。

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