RIOK2 phosphorylation by RSK promotes synthesis of the human small ribosomal subunit

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Cerezo, Emilie, L | Houles, Thibault | Lié, Oriane | Sarthou, Marie-Kerguelen | Audoynaud, Charlotte | Lavoie, Geneviève | Halladjian, Maral | Cantaloube, Sylvain | Froment, Carine | Burlet-Schiltz, Odile | Henry, Yves | Roux, Philippe, P | Henras, Anthony, K | Romeo, Yves

Edité par CCSD ; Public Library of Science -

International audience. Ribosome biogenesis lies at the nexus of various signaling pathways coordinating protein synthesis with cell growth and proliferation. This process is regulated by well-described transcriptional mechanisms, but a growing body of evidence indicates that other levels of regulation exist. Here we show that the Ras/mitogen-activated protein kinase (MAPK) pathway stimulates post-transcriptional stages of human ribosome synthesis. We identify RIOK2, a pre-40S particle assembly factor, as a new target of the MAPK-activated kinase RSK. RIOK2 phosphorylation by RSK stimulates cytoplasmic maturation of late pre-40S particles, which is required for optimal protein synthesis and cell proliferation. RIOK2 phosphorylation facilitates its release from pre-40S particles and its nuclear reimport, prior to completion of small ribosomal subunits. Our results bring a detailed mechanistic link between the Ras/MAPK pathway and the maturation of human pre-40S particles, which open a hitherto poorly explored area of ribosome biogenesis.

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