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A mechanism of target mRNA selection and activity regulation in meiosis-related RBM46-MEIOC-YTHDC2 complex

Ruixin Liang1,2, Qizi Chen1,2, Jiawei Li1,2

  • 1Department of Pediatric Laboratory, The Affiliated Children's Hospital of Jiangnan University, Wuxi 214023, China.

Iscience
|June 15, 2026
PubMed

Insights

The MEIOC complex, including RBM46 and YTHDC2, targets specific mRNAs like Rad21 for degradation during germ cell development. This complex regulates gene expression post-transcriptionally by controlling mRNA stability and recruitment of nucleases.

Area of Science:

  • Molecular and Cellular Biology
  • Reproductive Biology
  • RNA Biology

Background:

  • MEIOC, RBM46, and YTHDC2 are posttranscriptional regulators crucial for mammalian germ cell development.
  • The precise mechanism of mRNA target selection and degradation by the MEIOC complex remains unclear.

Purpose of the Study:

  • To elucidate the molecular mechanisms of target mRNA selection and degradation mediated by the MEIOC complex.
  • To investigate the roles of RBM46, MEIOC, and YTHDC2 in posttranscriptional regulation during germ cell development.

Main Methods:

  • Demonstrated binding of RBM46/MEIOC/YTHDC2 to Rad21 and Meioc 3'UTRs in cultured somatic cells.
  • Investigated the stabilization of MEIOC by YTHDC2 via inhibition of ubiquitination.
  • Characterized the interaction domains within the MEIOC complex and its association with target mRNAs and XRN2.

Main Results:

  • The MEIOC complex directly binds to and targets Rad21 and Meioc transcripts for degradation.
  • YTHDC2 stabilizes MEIOC by preventing its ubiquitination, while MEIOC's coiled-coil domain mediates complex formation.
  • MEIOC recruits the cytoplasmic ribonuclease XRN2 for mRNA degradation, with target mRNA facilitating RBM46-YTHDC2 interaction.

Conclusions:

  • MEIOC acts as a central component for selecting RNA-binding proteins and recruiting XRN2 for mRNA degradation.
  • The MEIOC complex regulates its own activity and target gene expression by modulating mRNA and protein stability.
  • This study reveals a novel mechanism for posttranscriptional control in germ cell development involving mRNA degradation.
Keywords:
Molecular mechanism of gene regulationMolecular network

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