m6A modification of a 3′ UTR site reduces RME1 mRNA levels to promote meiosis

G. Guy Bushkin (), David Pincus, Jeffrey T. Morgan, Kris Richardson, Caroline Lewis, Sze Ham Chan, David P. Bartel and Gerald R. Fink ()
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G. Guy Bushkin: Whitehead Institute for Biomedical Research
David Pincus: Whitehead Institute for Biomedical Research
Jeffrey T. Morgan: Whitehead Institute for Biomedical Research
Kris Richardson: Whitehead Institute for Biomedical Research
Caroline Lewis: Whitehead Institute for Biomedical Research
Sze Ham Chan: Whitehead Institute for Biomedical Research
David P. Bartel: Whitehead Institute for Biomedical Research
Gerald R. Fink: Whitehead Institute for Biomedical Research

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: Abstract Despite the vast number of modification sites mapped within mRNAs, known examples of consequential mRNA modifications remain rare. Here, we provide multiple lines of evidence to show that Ime4p, an N6-methyladenosine (m6A) methyltransferase required for meiosis in yeast, acts by methylating a site in the 3′ UTR of the mRNA encoding Rme1p, a transcriptional repressor of meiosis. Consistent with this mechanism, genetic analyses reveal that IME4 functions upstream of RME1. Transcriptome-wide, RME1 is the primary message that displays both increased methylation and reduced expression in an Ime4p-dependent manner. In yeast strains for which IME4 is dispensable for meiosis, a natural polymorphism in the RME1 promoter reduces RME1 transcription, obviating the requirement for methylation. Mutation of a single m6A site in the RME1 3′ UTR increases Rme1p repressor production and reduces meiotic efficiency. These results reveal the molecular and physiological consequences of a modification in the 3′ UTR of an mRNA.

Date: 2019
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DOI: 10.1038/s41467-019-11232-7

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