Microprocessor mediates transcriptional termination of long noncoding RNA transcripts hosting microRNAs

被引：114

作者：

Dhir, Ashish ^{[1
]}

Dhir, Somdutta ^{[1
]}

Proudfoot, Nick J. ^{[1
]}

Jopling, Catherine L. ^{[2
]}

机构：

[1] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England

[2] Univ Nottingham, Sch Pharm, Nottingham NG7 2RD, England

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2015年 / 22卷 / 04期

基金：

英国惠康基金; 欧洲研究理事会; 英国生物技术与生命科学研究理事会;

关键词：

POLYMERASE-II; ELONGATION COMPLEX; HUMAN GENOME; POLYADENYLATION; EXPRESSION; GENES; PROMOTER; BIOGENESIS; PRECURSORS; SITES;

D O I：

10.1038/nsmb.2982

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

MicroRNAs (miRNAs) play a major part in the post-transcriptional regulation of gene expression. Mammalian miRNA biogenesis begins with cotranscriptional cleavage of RNA polymerase II (Pol II) transcripts by the Microprocessor complex. Although most miRNAs are located within introns of protein-coding transcripts, a substantial minority of miRNAs originate from long noncoding (lnc) RNAs, for which transcript processing is largely uncharacterized. We show, by detailed characterization of liver-specific lnc-pri-miR-122 and genome-wide analysis in human cell lines, that most lncRNA transcripts containing miRNAs (lnc-pri-miRNAs) do not use the canonical cleavage-and-polyadenylation pathway but instead use Microprocessor cleavage to terminate transcription. Microprocessor inactivation leads to extensive transcriptional readthrough of lnc-pri-miRNA and transcriptional interference with downstream genes. Consequently we define a new RNase III-mediated, polyadenylation-independent mechanism of Pol II transcription termination in mammalian cells.

引用

页码：319 / +

页数：11

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