m6A reader Pho92 is recruited co-transcriptionally and couples translation efficacy to mRNA decay to promote meiotic fitness in yeast [iCLIP_miCLIP-seq]

During meiosis, in Saccharomyces cerevisiae, N6-methyladenosine (m6A) modified transcripts are induced, of which the function is unknown. Here, we uncover the role of the m6A reader Pho92. Cross-linking immunoprecipitation (CLIP) revealed that Pho92 associates with meiotic mRNAs in both m6A dependent and independent manner. Incidentally, Pho92 resides in the nucleus during early meiosis and associates with nascent RNAs, which is mediated through its interaction with Paf1C. Transcripts bound by Pho92 show elevated translational efficiency while cells lacking Pho92 display a small, but notable, increase in mRNA levels but not in protein levels, suggesting role of Pho92 in translation and decay. We show that Pho92 associates with ribosomes where it promotes the decay of m6A modified transcripts, contingent on active translation and the CCR4-NOT complex. We propose that m6A reader Pho92 is loaded co-transcriptionally to promote translation and subsequent decay fate of m6A modified transcripts, which ensures gamete fitness. Overall design: iCLIP and miCLIP analysis of Saccharomyces cerevisiae cells entering meiosis. iCLIP was performed for Pho92 and Gis2 tagged cells. To indentify m6A depending binding we used wild type and ime4 deletion mutant for the analysis. miCLIP was performed in WT and ime4 deletion strain.