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The S. cerevisiae m6A-reader Pho92 promotes timely meiotic recombination by controlling key methylated transcripts

Authors :
Jérémy Scutenaire
Damien Plassard
Mélody Matelot
Tommaso Villa
Julie Zumsteg
Domenico Libri
Bertrand Séraphin
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC)
Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Institut Jacques Monod (IJM (UMR_7592))
Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Institut de biologie moléculaire des plantes (IBMP)
Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)
Villa, Tommaso
Source :
Nucleic Acids Research, Nucleic Acids Research, In press, ⟨10.1093/nar/gkac640⟩
Publication Year :
2022

Abstract

N6-Methyladenosine (m6A), one of the most abundant internal modification of eukaryotic mRNAs, participates in the post-transcriptional control of gene expression through recruitment of specific m6A readers. In Saccharomyces cerevisiae, the m6A methyltransferase Ime4 is expressed only during meiosis and its deletion impairs this process. To elucidate how m6A control gene expression, we investigated the function of the budding yeast m6A reader Pho92. We show that Pho92 is an early meiotic factor that promotes timely meiotic progression. High-throughput RNA sequencing and mapping of Pho92-binding sites following UV-crosslinking reveal that Pho92 is recruited to specific mRNAs in an m6A-dependent manner during the meiotic prophase, preceding their down-regulation. Strikingly, point mutations altering m6A sites in mRNAs targeted by Pho92 are sufficient to delay their down-regulation and, in one case, to slow down meiotic progression. Altogether, our results indicate that Pho92 facilitate the meiotic progression by accelerating the down-regulation of timely-regulated mRNAs during meiotic recombination.mRNAs molecules carry information contained in genes to direct the formation of proteins. In specific circumstances, the cellular machinery modifies some mRNAs through the formation of m6A residues. To understand the function of these m6A marks, the authors used the yeast Saccharomyces cerevisiae in which their formation only occurs during meiosis that leads to spore formation. Characterization of the Pho92 protein that specifically recognizes m6A residues revealed its importance for meiosis. m6A sites bound by Pho92 were identified and shown to be biologically functional. Unexpectedly, Pho92 was found to regulate an early step of meiosis by controlling DNA recombination. Overall, this study provides important clues on the role of m6A residues in mRNAs.

Details

ISSN :
13624962 and 03051048
Database :
OpenAIRE
Journal :
Nucleic acids research
Accession number :
edsair.doi.dedup.....eb31f5e62104eb8b6cac25d1b605e6b7