An extensive program of periodic alternative splicing linked to cell cycle progression

Area of Science:

• Molecular Biology
• Genetics
• Cell Biology

Background:

• Cell cycle progression relies on precise temporal regulation of gene function.
• The role of alternative splicing (AS) in cell cycle temporal control remains largely unexplored.

Purpose of the Study:

• To investigate the role of alternative splicing in cell cycle regulation.
• To identify genes with cell cycle-dependent alternative splicing.
• To elucidate the regulatory mechanisms underlying cell cycle-dependent AS.

Main Methods:

• Sequencing the human transcriptome across two continuous cell cycles.
• Bioinformatic analysis to identify differentially spliced genes.
• Investigating the role of SR protein kinase CLK1 in regulating AS.

Main Results:

• Identified approximately 1300 genes with cell cycle-dependent AS changes.
• These genes are enriched in cell cycle control functions and distinct from genes with fluctuating transcript levels.
• CLK1 regulates a significant portion of these periodically spliced genes through an auto-inhibitory circuit.

Conclusions:

• Alternative splicing represents a major regulatory layer for cell cycle control.
• CLK1-mediated periodic AS is intimately linked to cell cycle progression.
• Dysregulation of CLK1 leads to cell cycle defects and is implicated in cancer.