National Institutes of Health, Bethesda MD 20892, USA"The S. cerevisiae m6A reader Pho92 promotes timely meiotic recombination by controlling key methylated transcripts."
Nucleic Acids Research, 51:517-535 https://doi.org/10.1093/nar/gkac640Jérémy Scutenaire, Damien Plassard, Mélody Matelot, Tommaso Villa, Julie Zumsteg, Domenico Libri, Bertrand Séraphin
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Jérémy Scutenaire, 32 years-old, has a PhD of molecular biology from the University of Perpignan. He is mainly interested in the role of RNA-binding proteins and their impact on the post-transcriptional regulation of gene expression. More precisely, he characterized a specific family of proteins that bind mRNAs through the presence of N6-methyladenosine, or m6A, which is one of the most abundant chemical modifications present in mRNA. He obtained his PhD in the team of Dr Bousquet-Antonelli (Laboratory of Plant Genom and Development, Perpignan, France) where he conducted pioneer works on the function of one of these particular proteins in development and heat stress response in plants. He then joined the team led by Dr Bertrand Séraphin (Institute of Genetics and Molecular and Cellular Biology, in the surrounding of Strasbourg) to pursue his post-doctoral researches on the role of one m6A-binding protein in the budding yeast. He showed that this protein accelerates the meiosis, by binding few hundreds of m6A-modified mRNAs and by temporally regulating the quantity of these transcripts. The high-throughput identification of mRNA targets of this protein highlights the importance of specific m6A sites and allowed to better understand the impact of these chemical modifications on the gametogenesis process. He recently joined the team of Dr Markus Hafner (National Institutes of Health, Bethesda, Etats-Unis) to characterize other types of RNA-binding proteins in human cells.
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Summary of the article:
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.
