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

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

doi:10.1371/journal.pgen.1009583

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

PLoS Genet. 2021 Jun 14;17(6):e1009583. doi: 10.1371/journal.pgen.1009583. eCollection 2021 Jun.

Authors

Affiliations

¹ Molecular, Cellular and Developmental biology department (MCD), Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, Toulouse, France.
² Institute for Research in Immunology and Cancer, Université de Montréal, Montreal, Québec, Canada.
³ Institut de Pharmacologie et Biologie Structurale (IPBS), Université de Toulouse, UPS, CNRS, Toulouse, France.
⁴ Department of Pathology and Cell Biology, Faculty of Medicine, Université de Montréal, Montreal, Québec, Canada.

Abstract

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 re-import, 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 opens a hitherto poorly explored area of ribosome biogenesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

HEK293 Cells
Humans
Mitogen-Activated Protein Kinases / metabolism*
Mutation
Phosphorylation
Protein Serine-Threonine Kinases / metabolism*
Protein Transport
Ribosome Subunits, Small / metabolism
Signal Transduction
Substrate Specificity
Transcription, Genetic

Substances

Protein Serine-Threonine Kinases
RIOK2 protein, human
Mitogen-Activated Protein Kinases

Grants and funding

The Henry/Henras group is supported by grants from ANR (to A.H.) and Ligue Contre le Cancer (to Y.R.). The work was also supported in part by the Région Midi-Pyrénées, European funds (Fonds Européens de Développement Régional, FEDER), Toulouse Métropole, and by the French Ministry of Research with the Investissement d’Avenir Infrastructures Nationales en Biologie et Santé program (ProFI, Proteomics French Infrastructure project, ANR-10-INBS-08, to O. B.-S.). This work was also supported by grants from the Canadian Institutes for Health Research (MOP-142374 and PJT-152995 to P.P.R.), and the Natural Sciences and Engineering Research Council of Canada (to P.P.R.). P.P.R. is a scholar of the Fonds de la recherche du Québec - Santé (FRQS). E.C. is supported by a fellowship from the French Ministry of Higher Education and Research. URLs: https://anr.fr/, https://www.ligue-cancer.net/, https://cihr-irsc.gc.ca/e/193.html, http://www.frqs.gouv.qc.ca/ The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.