Kar4, the yeast homolog of METTL14, is required for mRNA m < sup > 6 < /sup > A methylation and meiosis

by Zachory M. Park, Abigail J. Sporer, Katherine Kraft, Krystal K. Lum, Edith Blackman, Ethan Belnap, Christopher M. Yellman, Mark D. RoseKAR4, the yeast homolog of the mammalian mRNA N6A-methyltransferase complex componentMETTL14, is required for two disparate developmental programs inSaccharomyces cerevisiae: mating and meiosis. To understandKAR4’s role in yeast mating and meiosis, we used a genetic screen to isolate 25 function-specific mutant alleles, which map to non-overlapping surfaces on a predicted structure of the Kar4 protein (Kar4p). Most of the mating-specific alleles (Mat-) abolish Kar4p ’s interaction with the transcription factor Ste12p, indicating that Kar4p’s mating function is through Ste12p. In yeast, the mRNA methyltransferase complex was previously defined as comprising Ime4p (Kar4p’s paralog and the homolog of mammalian METTL3), Mum2p (homolog of mammalian WTAP), and Slz1p (MIS), but not Kar4p. During meiosis, Kar4p interacts with Ime4p, Mum2p, and Slz1p. Moreover, cells lacking Kar4p have highly reduced levels of mRNA methylation during meiosis indicating that Kar4p is a key member of the methyltransferase complex, as it is in humans. Analysis ofkar4Δ/Δ and 7 meiosis-specific alleles (Mei-) revealed that Kar4p is required early in meiosis, before initiation of S-phase and meiotic recombination. High copy expression of the meiotic transcriptional activatorIME1 rescued the defect of these Mei- alleles. Surprisingly, Kar4p was also found to be r...

Source: PLoS Genetics - August 21, 2023 Category: Genetics & Stem Cells Authors: Zachory M. Park Source Type: research