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

Silvia Bottini, Nedra Hamouda-Tekaya, Raphael Mategot, Laure-Emmanuelle Zaragosi, Stephane Audebert, Sabrina Pisano, Valerie Grandjean, Claire Mauduit, Mohamed Benahmed, Pascal Barbry, Emanuela Repetto and Michele Trabucchi ()
Additional contact information
Silvia Bottini: INSERM U1065, C3M, Team Control of Gene Expression (10)
Nedra Hamouda-Tekaya: INSERM U1065, C3M, Team Control of Gene Expression (10)
Raphael Mategot: INSERM U1065, C3M, Team Control of Gene Expression (10)
Laure-Emmanuelle Zaragosi: Université Côte d’Azur, CNRS, IPMC
Stephane Audebert: CRCM, Marseille Protéomique, Institut Paoli-Calmettes, Aix Marseille University, INSERM, CNRS
Sabrina Pisano: Université Côte d’Azur, CNRS, INSERM, IRCAN
Valerie Grandjean: INSERM U1065, C3M, Team Control of Gene Expression (10)
Claire Mauduit: INSERM U1065, C3M, Team Control of Gene Expression (10)
Mohamed Benahmed: Université Côte d’Azur, INSERM, C3M
Pascal Barbry: Université Côte d’Azur, CNRS, IPMC
Emanuela Repetto: INSERM U1065, C3M, Team Control of Gene Expression (10)
Michele Trabucchi: INSERM U1065, C3M, Team Control of Gene Expression (10)

Nature Communications, 2017, vol. 8, issue 1, 1-16

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-01126-x

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