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

Author

Listed:
  • Silvia Bottini

    (INSERM U1065, C3M, Team Control of Gene Expression (10)
    Université Côte d’Azur, INSERM, C3M)

  • Nedra Hamouda-Tekaya

    (INSERM U1065, C3M, Team Control of Gene Expression (10)
    Université Côte d’Azur, INSERM, C3M)

  • Raphael Mategot

    (INSERM U1065, C3M, Team Control of Gene Expression (10)
    Université Côte d’Azur, INSERM, C3M)

  • 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)
    Université Côte d’Azur, INSERM, C3M)

  • Claire Mauduit

    (INSERM U1065, C3M, Team Control of Gene Expression (10)
    Université Côte d’Azur, INSERM, C3M
    Université Lyon 1, UFR Médecine Lyon Sud
    Hospices Civils de Lyon, Hopital Lyon Sud, Laboratoire d’Anatomie et de Cytologie Pathologiques)

  • Mohamed Benahmed

    (Université Côte d’Azur, INSERM, C3M
    Centre Hospitalier Universitaire de Nice, Département de Recherche Clinique et d’Innovation)

  • Pascal Barbry

    (Université Côte d’Azur, CNRS, IPMC)

  • Emanuela Repetto

    (INSERM U1065, C3M, Team Control of Gene Expression (10)
    Université Côte d’Azur, INSERM, C3M)

  • Michele Trabucchi

    (INSERM U1065, C3M, Team Control of Gene Expression (10)
    Université Côte d’Azur, INSERM, C3M)

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.

Suggested Citation

  • Silvia Bottini & Nedra Hamouda-Tekaya & Raphael Mategot & Laure-Emmanuelle Zaragosi & Stephane Audebert & Sabrina Pisano & Valerie Grandjean & Claire Mauduit & Mohamed Benahmed & Pascal Barbry & Emanu, 2017. "Post-transcriptional gene silencing mediated by microRNAs is controlled by nucleoplasmic Sfpq," Nature Communications, Nature, vol. 8(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01126-x
    DOI: 10.1038/s41467-017-01126-x
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    Cited by:

    1. Laura A. Murray-Nerger & Clarisel Lozano & Eric M. Burton & Yifei Liao & Nathan A. Ungerleider & Rui Guo & Benjamin E. Gewurz, 2024. "The nucleic acid binding protein SFPQ represses EBV lytic reactivation by promoting histone H1 expression," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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