RT Journal Article SR Electronic T1 ketu mutant mice uncover an essential meiotic function for the ancient, putative RNA helicase YTHDC2 JF bioRxiv FD Cold Spring Harbor Laboratory SP 171827 DO 10.1101/171827 A1 Devanshi Jain A1 M. Rhyan Puno A1 Kathryn V. Anderson A1 Scott Keeney YR 2017 UL http://biorxiv.org/content/early/2017/08/06/171827.abstract AB Mechanisms regulating mammalian meiotic progression are poorly understood. Here we identify mouse YTHDC2 as a critical component of this regulation. A screen yielded a mutant, “ketu”, with male and female sterility caused by a Ythdc2 missense mutation. Mutant germ cells enter meiosis but proceed prematurely to aberrant metaphase and apoptosis. ketu phenocopies mutants lacking MEIOC, a YTHDC2 partner. YTHDC2 is cytoplasmic and a YTH domain solution structure reveals conservation of a hydrophobic N6-methyladenosine recognition pocket, consistent with roles in post-transcriptional regulation. Orthologs are present throughout metazoans, but are structurally diverged in nematodes and, more dramatically, in Drosophilidae, where Bgcn is a biochemically distinct descendant of a Ythdc2 gene duplication. We also uncover similarity between MEIOC and Bam, a Bgcn partner unique to schizophoran flies. We propose that regulation of gene expression by the YTHDC2-MEIOC complex is an evolutionarily ancient strategy for controlling the germline transition from mitosis to meiosis.