Quantitative microarray profiling provides evidence against widespread coupling of alternative splicing with nonsense-mediated mRNA decay to control gene expression
- Qun Pan1,6,
- Arneet L. Saltzman1,2,6,
- Yoon Ki Kim5,
- Christine Misquitta1,
- Ofer Shai3,
- Lynne E. Maquat5,
- Brendan J. Frey1,3, and
- Benjamin J. Blencowe1,2,4,7
- 1Banting and Best Department of Medical Research, 2Department of Molecular and Medical Genetics, 3Department of Electrical and Computer Engineering, 4Program in Proteomics and Bioinformatics, University of Toronto, Ontario, M5G 1L6, Canada; 5Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, Rochester, New York 14642, USA
Abstract
Sequence-based analyses have predicted that ∼35% of mammalian alternative splicing (AS) events produce premature termination codon (PTC)-containing splice variants that are targeted by the process of nonsense-mediated mRNA decay (NMD). This led to speculation that AS may often regulate gene expression by activating NMD. Using AS microarrays, we show that PTC-containing splice variants are generally produced at uniformly low levels across diverse mammalian cells and tissues, independently of the action of NMD. Our results suggest that most PTC-introducing AS events are not under positive selection pressure and therefore may not contribute important functional roles.
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Footnotes
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Supplemental material is available at http://www.genesdev.org and http://www.utoronto.ca/intron/AS.
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Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1382806.
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↵6 These authors contributed equally to this work.
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↵7 Corresponding author. E-MAIL b.blencowe{at}utoronto.ca; FAX (416) 978-8528.
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- Accepted November 23, 2005.
- Received October 11, 2005.
- Cold Spring Harbor Laboratory Press
