期刊
NATURE COMMUNICATIONS
卷 8, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-017-01126-x
关键词
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资金
- AVENIR program of INSERM
- Marie Curie CIG
- ANR through the Investments for the Future [ANR-11-LABX-0028-01]
- ITMO cancer of Avesian [ProstaMir P029393]
- INSERM-PACA region fellowship
- FRM [DEQ20140329551, DEQ20130326464, ING20140129224]
- Institut Paoli-Calmettes
- Canceropole PACA
- ARC
- IBiSA
- Conseil General 06 de la Region PACA
- ANR [ANR-11-LABX-0028-01, ANR-10-INBS-09-03, ANR-10-INBS-09-02]
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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