Posttranscriptional Regulation of miRNAs Harboring Conserved Terminal Loops

被引：273

作者：

Michlewski, Gracjan ^{[1
]}

Guil, Sonia ^{[1
,2
]}

Semple, Colin A. ^{[1
]}

Caceres, Javier F. ^{[1
]}

机构：

[1] Western Gen Hosp, Inst Genet & Mol Med, Med Res Council Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland

[2] Catalan Inst Oncol ICO IDIBELL, Canc Epigenet & Biol Program PEBC, Barcelona 08907, Catalonia, Spain

来源：

MOLECULAR CELL | 2008年 / 32卷 / 03期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

D O I：

10.1016/j.molcel.2008.10.013

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：

We recently found that hnRNP A1, a protein implicated in many aspects of RNA processing, acts as an auxiliary factor for the Drosha-mediated processing of a microRNA precursor, pri-miR-18a. Here, we provide the mechanism by which hnRNP A1 regulates this event. We show that hnRNP A1 binds to the loop of pri-miR-18a and induces a relaxation at the stem, creating a more favorable cleavage site for Drosha. We found that approximately 14% of all pri-miRNAs have highly conserved loops, which we predict act as landing pads for trans-acting factors influencing miRNA processing. In agreement, we show that 2'O-methyl oligonucleotides targeting conserved loops (LooptomiRs) abolish miRNA processing in vitro. Furthermore, we present evidence to support an essential role of conserved loops for pri-miRNA processing. Altogether, these data suggest the existence of auxiliary factors for the processing of specific miRNAs, revealing an additional level of complexity for the regulation of miRNA biogenesis.

引用

页码：383 / 393

页数：11

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