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

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.