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ketu mutant mice uncover an essential meiotic function for the ancient RNA helicase YTHDC2.

Titleketu mutant mice uncover an essential meiotic function for the ancient RNA helicase YTHDC2.
Publication TypeJournal Article
Year of Publication2018
AuthorsJain D, M Puno R, Meydan C, Lailler N, Mason CE, Lima CD, Anderson KV, Keeney S
JournalElife
Volume7
Date Published2018 Jan 23
ISSN2050-084X
Abstract

Mechanisms regulating mammalian meiotic progression are poorly understood. Here we identify mouse YTHDC2 as a critical component. A screen yielded a sterile mutant, '', caused by amissense mutation. Mutant germ cells enter meiosis but proceed prematurely to aberrant metaphase and apoptosis, and display defects in transitioning from spermatogonial to meiotic gene expression programs.phenocopies mutants lacking MEIOC, a YTHDC2 partner. Consistent with roles in post-transcriptional regulation, YTHDC2 is cytoplasmic, has 3'→5' RNA helicase activity in vitro, and has similarity within its YTH domain to an-methyladenosine recognition pocket. Orthologs are present throughout metazoans, but are diverged in nematodes and, more dramatically, Drosophilidae, where Bgcn is descended from agene duplication. We also uncover similarity between MEIOC and Bam, a Bgcn partner unique to schizophoran flies. We propose that regulation of gene expression by YTHDC2-MEIOC is an evolutionarily ancient strategy for controlling the germline transition into meiosis.

DOI10.7554/eLife.30919
Alternate JournalElife
PubMed ID29360036
Grant ListR37 HD035455 / / Eunice Kennedy Shriver National Institute of Child Health and Human Development /
P30 CA008748 / / National Cancer Institute /
R35 GM118080 / / National Institute of General Medical Sciences /
I9-A9-071 / / Starr Cancer Consortium /
NNX14AH50G 15-15Omni2-0063 / / National Aeronautics and Space Administration /
OPP1151054 / / Bill and Melinda Gates Foundation /
P30 CA008748 / CA / NCI NIH HHS / United States
R37 HD035455 / HD / NICHD NIH HHS / United States
R35 GM118080 / GM / NIGMS NIH HHS / United States