Regulation of microRNA-mediated gene silencing by microRNA precursors.

Abstract:

:Processing of microRNAs (miRNAs) from their precursors to their biologically active mature forms is regulated during development and cancer. We show that mouse pri- or pre-miR-151 can bind to and compete with mature miR-151-5p and miR-151-3p for binding sites contained within the complementary regions of the E2f6 mRNA 3' untranslated region (UTR). E2f6 mRNA levels were directly regulated by pri- or pre-miR-151. Conversely, miR-151-mediated repression of ARHGDIA mRNA was dependent on the level of mature miR-151 because only the mature miRNA binds the 3' UTR. Thus, processing of miR-151 can have different effects on separate mRNA targets within a cell. A bioinformatics pipeline revealed additional candidate regions where precursor miRNAs can compete with their mature miRNA counterparts. We validated this experimentally for miR-124 and the SNAI2 3' UTR. Hence, miRNA precursors can serve as post-transcriptional regulators of miRNA activity and are not mere biogenesis intermediates.

journal_name

Nat Struct Mol Biol

authors

Roy-Chaudhuri B,Valdmanis PN,Zhang Y,Wang Q,Luo QJ,Kay MA

doi

10.1038/nsmb.2862

subject

Has Abstract

pub_date

2014-09-01 00:00:00

pages

825-32

issue

9

eissn

1545-9993

issn

1545-9985

pii

nsmb.2862

journal_volume

21

pub_type

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