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Nat Commun. 2017 Oct 30;8(1):1189. doi: 10.1038/s41467-017-01126-x.

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

Author information

1
INSERM U1065, C3M, Team Control of Gene Expression (10), 151 route de St-Antoine-de-Ginestière, B.P. 2 3194, Nice, 06204, France.
2
Université Côte d'Azur, INSERM, C3M, 151 route de St-Antoine-de-Ginestière, B.P. 2 3194, Nice, 06204, France.
3
Université Côte d'Azur, CNRS, IPMC, Valbonne, France.
4
CRCM, Marseille Protéomique, Institut Paoli-Calmettes, Aix Marseille University, INSERM, CNRS, 27 bd Leï Roure, BP 30059, Marseille, 13273, France.
5
Université Côte d'Azur, CNRS, INSERM, IRCAN, Faculty of Medicine, 28 Av. Valombrose, Nice, 06107, France.
6
Université Lyon 1, UFR Médecine Lyon Sud, Lyon, F-69921, France.
7
Hospices Civils de Lyon, Hopital Lyon Sud, Laboratoire d'Anatomie et de Cytologie Pathologiques, Pierre-Bénite, F-69495, France.
8
Centre Hospitalier Universitaire de Nice, Département de Recherche Clinique et d'Innovation, Nice, F-06001, France.
9
INSERM U1065, C3M, Team Control of Gene Expression (10), 151 route de St-Antoine-de-Ginestière, B.P. 2 3194, Nice, 06204, France. mtrabucchi@unice.fr.
10
Université Côte d'Azur, INSERM, C3M, 151 route de St-Antoine-de-Ginestière, B.P. 2 3194, Nice, 06204, France. mtrabucchi@unice.fr.

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.

PMID:
29084942
PMCID:
PMC5662751
DOI:
10.1038/s41467-017-01126-x
[Indexed for MEDLINE]
Free PMC Article

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