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RNPS1 in PSAP complex controls periodic pre-mRNA splicing over the cell cycle.

Kazuhiro Fukumura1, Akio Masuda2, Jun-Ichi Takeda2

  • 1Division of Gene Regulation, Oncology Innovation Center, Fujita Health University, Toyoake, Aichi 470-1192, Japan.

Iscience
|December 17, 2024
PubMed
Summary

RNPS1 protein controls periodic RNA splicing during the cell cycle. It functions within the PSAP complex to regulate cell cycle-dependent gene expression, with its levels controlled by the ubiquitin-proteasome pathway.

Keywords:
Cell biologyCellular physiologyMolecular biologyProperties of biomolecules

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Cell cycle progression relies on regulated gene expression, including precise splicing control.
  • The specific splicing factors governing cell cycle-dependent splicing remain largely unidentified.
  • Aurora kinase B (AURKB) gene expression is critical for cell division, involving regulated splicing.

Purpose of the Study:

  • To identify the splicing factor responsible for cell cycle-dependent splicing of the AURKB gene.
  • To elucidate the mechanism by which this splicing factor operates and is regulated.
  • To determine the broader role of this splicing factor in regulating gene expression throughout the cell cycle.

Main Methods:

  • Whole-transcriptome sequencing was performed on cells deficient in RNPS1 and PNN.
  • Immunoblotting and proteasome inhibition assays were used to assess RNPS1 protein levels and regulation.
  • Analysis of splicing patterns in specific introns, including AURKB intron 5, was conducted.

Main Results:

  • RNPS1, in complex with PNN and SAP18 (PSAP complex), is essential for the precise splicing of specific introns, notably AURKB intron 5.
  • RNPS1, alone or in the PSAP complex, acts as a crucial splicing factor for a subset of introns.
  • RNPS1 protein levels are cyclically regulated and decrease via the ubiquitin-proteasome pathway, correlating with periodic splicing events.

Conclusions:

  • RNPS1 is a key splicing factor that orchestrates periodic splicing during the cell cycle.
  • The PSAP complex, involving RNPS1, is critical for cell cycle-dependent splicing.
  • Regulation of RNPS1 protein stability by the ubiquitin-proteasome pathway is essential for its role in cyclical gene expression.