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A SUMO-dependent feedback loop senses and controls the biogenesis of nuclear pore subunits

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  • Jérôme O. Rouvière

    (Sorbonne Paris Cité
    Aarhus University)

  • Manuel Bulfoni

    (CNRS)

  • Alex Tuck

    (University of Edinburgh
    Friedrich Miescher Institute for Biomedical Research)

  • Bertrand Cosson

    (CNRS)

  • Frédéric Devaux

    (Laboratoire de biologie computationnelle et quantitative, LCQB)

  • Benoit Palancade

    (Sorbonne Paris Cité)

Abstract

While the activity of multiprotein complexes is crucial for cellular metabolism, little is known about the mechanisms that collectively control the expression of their components. Here, we investigate the regulations targeting the biogenesis of the nuclear pore complex (NPC), the macromolecular assembly mediating nucleocytoplasmic exchanges. Systematic analysis of RNA-binding proteins interactomes, together with in vivo and in vitro assays, reveal that a subset of NPC mRNAs are specifically bound by Hek2, a yeast hnRNP K-like protein. Hek2-dependent translational repression and protein turnover are further shown to finely tune the levels of NPC subunits. Strikingly, mutations or physiological perturbations altering pore integrity decrease the levels of the NPC-associated SUMO protease Ulp1, and trigger the accumulation of sumoylated versions of Hek2 unable to bind NPC mRNAs. Our results support the existence of a quality control mechanism involving Ulp1 as a sensor of NPC integrity and Hek2 as a repressor of NPC biogenesis.

Suggested Citation

  • Jérôme O. Rouvière & Manuel Bulfoni & Alex Tuck & Bertrand Cosson & Frédéric Devaux & Benoit Palancade, 2018. "A SUMO-dependent feedback loop senses and controls the biogenesis of nuclear pore subunits," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03673-3
    DOI: 10.1038/s41467-018-03673-3
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