May 2018: A feedback loop adjusting the biogenesis of a multiprotein complex
Numerous cellular processes rely on the function of multiprotein complexes, yet little is known about the regulations that control their homeostasis. A group of scientists, leaded by Benoit Palancade at Institut Jacques Monod, have used the nuclear pore complex (NPC) as a paradigm to decipher the mechanisms that sustain the timely biogenesis of such stoichiometric assemblies. Their work, published in this month issue of Nature communications, reveals a feedback loop by which the biogenesis of NPC subunits is sensed and controlled depending on the integrity of the whole complex.
In order to unravel novel mechanisms controlling the biogenesis of multiprotein complexes, the authors have analyzed a large panel of datasets reporting the association of RNA-binding proteins to their target mRNAs in budding yeast. Focusing on the transcripts encoding the subunits of the NPC, they found that a subset of the mRNAs encoding FG-repeat containing NPC proteins are specifically bound by Hek2, a hnRNP E/K-related protein. Hek2-dependent translational repression and protein degradation were further shown to finely tune the levels of NPC subunits, preventing the accumulation of unassembled, aggregation-prone polypeptides.
Strikingly, the authors found that this repressive activity could be alleviated in response to an increased cellular demand for NPC subunits. Indeed, mutant or physiological perturbations altering pore integrity were found to decrease the activity of a NPC-associated SUMO protease, further triggering the accumulation of sumoylated versions of Hek2 unable to bind NPC mRNAs. These studies supports a model in which the SUMO protease and the translational repressor are respectively the sensor and the effector of a quality control mechanism maintaining complex integrity.
- For more information:
Rouvière JO, Bulfoni M, Tuck A, Cosson B, Devaux F & Palancade B.
A SUMO-dependent feedback loop senses and controls the biogenesis of nuclear pore subunits
Nature Communications April 25 2018