Post-transcriptional Gene Silencing Mediated by MicroRNAs is Controlled by Nucleoplasmic Sfpq

Overview

Journal Nat Commun

Specialty Biology

Date 2017 Nov 1

PMID 29084942

Citations 45

Authors

Silvia Bottini

Nedra Hamouda-Tekaya

Raphael Mategot

Laure-Emmanuelle Zaragosi

Stephane Audebert

Sabrina Pisano

Valerie Grandjean

Claire Mauduit

Mohamed Benahmed

Pascal Barbry

Emanuela Repetto

Michele Trabucchi

Affiliations

Soon will be listed here.

Abstract

There is a growing body of evidence about the presence and the activity of the miRISC in the nucleus of mammalian cells. Here, we show by quantitative proteomic analysis that Ago2 interacts with the nucleoplasmic protein Sfpq in an RNA-dependent fashion. By a combination of HITS-CLIP and transcriptomic analyses, we demonstrate that Sfpq directly controls the miRNA targeting of a subset of binding sites by local binding. Sfpq modulates miRNA targeting in both nucleoplasm and cytoplasm, indicating a nucleoplasmic commitment of Sfpq-target mRNAs that globally influences miRNA modes of action. Mechanistically, Sfpq binds to a sizeable set of long 3'UTRs forming aggregates to optimize miRNA positioning/recruitment at selected binding sites, including let-7a binding to Lin28A 3'UTR. Our results extend the miRNA-mediated post-transcriptional gene silencing into the nucleoplasm and indicate that an Sfpq-dependent strategy for controlling miRNA activity takes place in cells, contributing to the complexity of miRNA-dependent gene expression control.

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