Transcriptomics,Genomics

Dataset Information

161

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. Overall design: mRNA profiles for wild-type and YTHDC2/BGCN testis at P12 and P14 were generated by sequencing. m6A modified transcripts were identified by immunopreciitation with an anti-m6A specific antibody followed by sequencing for P12 testes. RNAs interacting with YTHDC2/BGCN were identified by immunoprecipitation with a anti-YTHDC2/BGCN specific antibody followe by sequencing for P12 testes. All experiments were performed in duplicates.

INSTRUMENT(S): Illumina NextSeq 500 (Mus musculus)

SUBMITTER: Pedro J Batista  

PROVIDER: GSE93533 | GEO | 2017-11-15

SECONDARY ACCESSION(S): PRJNA361125

REPOSITORIES: GEO

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Publications

The conserved RNA helicase YTHDC2 regulates the transition from proliferation to differentiation in the germline.

Bailey Alexis S AS   Batista Pedro J PJ   Gold Rebecca S RS   Chen Y Grace YG   de Rooij Dirk G DG   Chang Howard Y HY   Fuller Margaret T MT  

eLife 20171031


The switch from mitosis to meiosis is the key event marking onset of differentiation in the germline stem cell lineage. In Drosophila, the translational repressor Bgcn is required for spermatogonia to stop mitosis and transition to meiotic prophase and the spermatocyte state. Here we show that the mammalian Bgcn homolog YTHDC2 facilitates a clean switch from mitosis to meiosis in mouse germ cells, revealing a conserved role for YTHDC2 in this critical cell fate transition. YTHDC2-deficient male  ...[more]

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