1. Cell Biology
Download icon

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

  1. Daniel Dominguez
  2. Yi-Hsuan Tsai
  3. Robert Weatheritt
  4. Yang Wang
  5. Benjamin J Blencowe
  6. Zefeng Wang  Is a corresponding author
  1. University of North Carolina at Chapel Hill, United States
  2. University of Toronto, Canada
Research Article
  • Cited 21
  • Views 3,682
  • Annotations
Cite this article as: eLife 2016;5:e10288 doi: 10.7554/eLife.10288

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

  1. Daniel Dominguez

    Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, United States
    Competing interests
    No competing interests declared.
  2. 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.
  3. Robert Weatheritt

    Donnelly Centre and Department of Molecular Genetics, University of Toronto, Toronto, Canada
    Competing interests
    No competing interests declared.
  4. Yang Wang

    Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, United States
    Competing interests
    No competing interests declared.
  5. Benjamin J Blencowe

    Donnelly Centre and Department of Molecular Genetics, University of Toronto, Toronto, Canada
    Competing interests
    Benjamin J Blencowe, Reviewing editor, eLIFE .
  6. 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.

Reviewing Editor

  1. Gene Yeo, University of California, San Diego, United States

Publication history

  1. Received: July 22, 2015
  2. Accepted: March 24, 2016
  3. Accepted Manuscript published: March 25, 2016 (version 1)
  4. Version of Record published: May 27, 2016 (version 2)

Copyright

© 2016, Dominguez et al.

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.

Metrics

  • 3,682
    Page views
  • 1,064
    Downloads
  • 21
    Citations

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

  1. Further reading

Further reading

    1. Cell Biology
    2. Neuroscience
    Eric A Prinslow et al.
    Research Article
    1. Cell Biology
    Diego Acosta-Alvear et al.
    Research Article Updated