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.
Highlights
Despite the vast number of modification sites mapped within mRNAs, known examples of consequential mRNA modifications remain rare
The presence of the RME1-S288C allele in most laboratory strains including S288C, Sigma127b, W303, and RM11 (Supplementary Fig. 1a) suggests that these strains have been selected for a strict mitosis–meiosis dichotomy
Our data show that the requirement for IME4 and its catalytic methyltransferase function for meiosis is dependent upon the particular allele of RME1 carried by a strain
Summary
Despite the vast number of modification sites mapped within mRNAs, known examples of consequential mRNA modifications remain rare. 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. 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. The decision to enter meiosis is controlled through multiple pathways that integrate nutritional and ploidy signals
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