Cited by 89MicroRNA in disease regulationRNA Research and SplicingPlant Molecular Biology Research

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

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Bottini, Silvia, Hamouda-Tekaya, Nedra, Mategot, Raphael, Zaragosi, Laure-Emmanuelle, Audebert, Stephane, Pisano, Sabrina, Grandjean, Valerie, Mauduit, Claire +4 more·2017·Nature Communications

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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  • Low molecular weight miRISC can interact with mRNAs within the nucleus and induce nuclear mRNA degradation.

    “It has been reported that low molecular weight miRISC can interact with mRNAs within the nucleus and induce nuclear mRNA degradation, although the mechanism behind this is unclear (59, 61, 63).”

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Authors
Bottini, S., Hamouda-Tekaya, N., Mategot, R., Zaragosi, L.-E., Audebert, S., Pisano, S., Grandjean, V., Mauduit, C., Benahmed, M., Barbry, P., Repetto, E., & Trabucchi, M.
Affiliations
  • Inserm (FR)
  • Centre National de la Recherche Scientifique (FR)
  • Lyon 1 Université (FR)
Venue
Nature Communications
Published
2017-10-30
Volume
8
Issue
1
Pages
1189-1189
ISSN
2041-1723 (ISSN-L)
OpenAlex
W2766537551
Cited by
89
References
72
Citations by year
2026: 2 · 2025: 5 · 2024: 9 · 2023: 14 · 2022: 16 · 2021: 13 · 2020: 14 · 2019: 6 · 2018: 10
FWCI
2.76
Type
journal article
Language
en
Update notices
addendum (2026-04-17)
Open access
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL AMU (submittedVersion, other-oa)
  • HAL (submittedVersion)
  • HAL Portal Artxiker (Hindustan Aeronautics Limited (India)) (submittedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Infrastructures en Biologie Santé et Agronomie
  • Agence Nationale de la Recherche (ANR‐10‐INBS‐09‐03, ANR- 10-INBS-09, ANR‐10‐INBS‐09‐02, ANR-10, 10-INBS-09, ANR-11-LABX-0028)
  • Institut National de la Santé et de la Recherche Médicale (ANR-11-LABX-0028-01)
  • Canceropôle PACA (ANR-11-LABX-0028-01)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
Keywords
SFPQ, microRNA-induced silencing complex, post-transcriptional gene silencing, miRNA targeting, nucleoplasm, Argonaute 2, 3' untranslated region, let-7a, LIN28A, HITS-CLIP, microRNA binding sites
MeSH terms
RAW 264.7 Cells, PTB-Associated Splicing Factor, Animals, Cell Nucleus, HeLa Cells, Humans, Protein Binding, RNA Processing, Post-Transcriptional, RNA-Binding Proteins, 3' Untranslated Regions, Gene Silencing, Gene Expression Profiling, MicroRNAs, Cell Line, Tumor, Mice, HEK293 Cells, Argonaute Proteins

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