Regulation of the transition from mitosis to meiosis by the conserved RNA-helicase YTHDC2/BGCN [RIP-Seq]

ABSTRACT: In the germline stem cell lineage, proliferating gonial cells switch from mitotic proliferation to meiotic prophase, marked by the onset of a cell-type-specific transcription program and a specialized cell cycle required to generate haploid gametes. The Drosophila gene benign gonial cell neoplasm (bgcn) encodes an RNA binding translational repressor required in fly testes for spermatogonia to stop dividing and transition to the spermatocyte state and meiosis. Here we show that the mammalian bgcn ortholog, YTHDC2, plays a key role in allowing a clean transition from mitosis to meiosis in both male and female germ cells in mouse, pointing towards a conserved role of post-transcriptional control of RNA translation and/or stability in this critical cell fate transition. Ythdc2-/- male germ cells undergo mitotic divisions but fail to properly execute meiotic prophase, instead attempting a mitotic-like division then undergoing cell death. Many meiotic markers were only weakly expressed in Ythdc2-/- testes compared to wild-type controls. Strikingly, the mitotic cyclin Cyclin A2, which is down-regulated prior to entry into meiotic prophase in wild-type, remained high in Ythdc2-/- germ cells that also expressed the meiotic marker SYCP3, suggesting that the mutant germ cells attempting to enter meiotic prophase have a mixed identity. YTHDC2 binds RNAs involved in both the mitotic cell cycle, including the mRNA Ccna2 that encodes Cyclin A2, as well as specific piRNA precursor RNAs and transcripts required for later stages of germ cell differentiation. YTHDC2-bound RNAs in testes were enriched for the m6A modification, suggesting that YTHDC2 may selectively regulate multiple target RNAs marked with m6A, to promote a clean transition from mitosis to meiosis and terminal differentiation.

ORGANISM(S): Mus musculus

PROVIDER: GSE93533 | GEO | 2017/11/15

SECONDARY ACCESSION(S): PRJNA361125

REPOSITORIES: GEO