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Nuclear m(6)A Reader YTHDC1 Regulates mRNA Splicing.

Wen Xiao1, Samir Adhikari1, Ujwal Dahal1

  • 1Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, CAS Center for Excellence in Molecular Cell Science, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.

Molecular Cell
|February 16, 2016
PubMed
Summary
This summary is machine-generated.

The nuclear protein YTHDC1 regulates mRNA splicing by recruiting SRSF3 and blocking SRSF10. This finding clarifies the role of N(6)-methyladenosine (m(6)A) in pre-mRNA processing.

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Area of Science:

  • Molecular Biology
  • RNA Biology
  • Epigenetics

Background:

  • The function of N(6)-methyladenosine (m(6)A) and its reader protein YTHDC1 in pre-mRNA splicing is not well understood.
  • m(6)A is a prevalent RNA modification impacting various cellular processes.

Purpose of the Study:

  • To elucidate the regulatory mechanism of YTHDC1 in pre-mRNA splicing.
  • To investigate the interaction between YTHDC1 and splicing factors SRSF3 and SRSF10.

Main Methods:

  • Transcriptome-wide analysis using PAR-CLIP-seq.
  • In vitro pull-down assays.
  • Nuclear speckle localization studies.

Main Results:

  • YTHDC1 promotes exon inclusion by recruiting SRSF3 and inhibiting SRSF10 binding.
  • YTHDC1-mediated splicing patterns mirror SRSF3 but oppose SRSF10.
  • YTHDC1 influences the localization and RNA-binding of SRSF3 and SRSF10.

Conclusions:

  • YTHDC1 acts as an m(6)A reader to modulate mRNA splicing.
  • YTHDC1 directly regulates splicing factors, impacting their access to target mRNAs.
  • This study provides direct evidence for YTHDC1's role in splicing regulation.