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

Abstract
Article and author information
Metrics

Abstract

Progression through the mitotic cell cycle requires periodic regulation of gene function at the levels of transcription, translation, protein-protein interactions, post-translational modification and degradation. However, the role of alternative splicing (AS) in the temporal control of cell cycle is not well understood. By sequencing the human transcriptome through two continuous cell cycles, we identify ~1,300 genes with cell cycle-dependent AS changes. These genes are significantly enriched in functions linked to cell cycle control, yet they do not significantly overlap genes subject to periodic changes in steady-state transcript levels. Many of the periodically spliced genes are controlled by the SR protein kinase CLK1, whose level undergoes cell cycle-dependent fluctuations via an auto-inhibitory circuit. Disruption of CLK1 causes pleiotropic cell cycle defects and loss of proliferation, whereas CLK1 over-expression is associated with various cancers. These results thus reveal a large program of CLK1-regulated periodic AS intimately associated with cell cycle control.

Article and author information

Author details

Daniel Dominguez

Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, United States

Competing interests
No competing interests declared.
Yi-Hsuan Tsai

Program in Bioinformatics and Computational Biology, University of North Carolina at Chapel Hill, Chapel Hill, United States

Competing interests
No competing interests declared.
Robert Weatheritt

Donnelly Centre and Department of Molecular Genetics, University of Toronto, Toronto, Canada

Competing interests
No competing interests declared.
Yang Wang

Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, United States

Competing interests
No competing interests declared.
Benjamin J Blencowe

Donnelly Centre and Department of Molecular Genetics, University of Toronto, Toronto, Canada

Competing interests
Benjamin J Blencowe, Reviewing editor, eLIFE .
Zefeng Wang

Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, United States

For correspondence
zefeng@med.unc.edu

Competing interests
No competing interests declared.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.