En direct

CRCM PhD Day 2021 will take place on May 28 2021 - Les mitochondries nouvelles cibles thérapeutiques potentielles dans le cancer du pancréas - La cycline A2, qui maintient l'homéostasie du côlon, est un facteur de pronostic dans le cancer colorectal -

10 2017 Nature communications

Post-transcriptional gene silencing mediated by microRNAs is controlled by nucleoplasmic Sfpq.


Bottini S, Hamouda-Tekaya N, Mategot R, Zaragosi LE, Audebert S, Pisano S, Grandjean V, Mauduit C, Benahmed M, Barbry P, Repetto E, Trabucchi M


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.

Lire l‘article