PT  - JOURNAL ARTICLE
AU  - Jérôme O. Rouvière
AU  - Manuel Bulfoni
AU  - Alex Tuck
AU  - Bertrand Cosson
AU  - Frédéric Devaux
AU  - Benoit Palancade
TI  - A SUMO-dependent feedback loop senses and controls the biogenesis of nuclear pore subunits
AID  - 10.1101/188441
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 188441
4099  - http://biorxiv.org/content/early/2017/09/13/188441.short
4100  - http://biorxiv.org/content/early/2017/09/13/188441.full
AB  - 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 in response to the cellular demand. Here, we have investigated 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, revealed that a subset of NPC mRNAs are specifically bound by Hek2, a yeast hnRNP K-like protein. Hek2-dependent NPC mRNAs translational repression and protein turnover are further shown to finely tune the levels of NPC subunits. Strikingly, Hek2 binding to its target mRNAs requires prior desumoylation by the NPC-associated SUMO protease Ulp1. Mutations or physiological perturbations altering NPC integrity lead to a decrease in the levels of active Ulp1 and to the accumulation of sumoylated, inactive forms of Hek2. 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.