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The Coupling of Alternative Splicing and Nonsense-Mediated mRNA Decay

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Alternative Splicing in the Postgenomic Era

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 623))

Abstract

Most human genes exhibit alternative splicing, but not all alternatively spliced transcripts produce functional proteins. Computational and experimental results indicate that a substantial fraction of alternative splicing events in humans result in mRNA isoforms that harbor a premature termination codon (PTC). These transcripts are predicted to be degraded by the nonsense-mediated mRNA decay (NMD) pathway. One explanation for the abundance of PTC-containing isoforms is that they represent splicing errors that are identified and degraded by the NMD pathway. Another potential explanation for this startling observation is that cells may link alternative splicing and NMD to regulate the abundance of mRNA transcripts. This mechanism, which we call “Regulated Unproductive Splicing and Translation” (RUST), has been experimentally shown to regulate expression of a wide variety of genes in many organisms from yeast to human. It is frequently employed for autoregulation of proteins that affect the splicing process itself. Thus, alternative splicing and NMD act together to play an important role in regulating gene expression.

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Authors and Affiliations

  1. Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, USA

    Liana F. Lareau & Angela N. Brooks

  2. Biophysics Graduate Group, University of California, Berkeley, Berkeley, California, USA

    David A. W. Soergel

  3. Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, California, USA

    Qi Meng

  4. Department of Molecular and Cell Biology Biophysics Graduate Group Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, California, USA

    Steven E. Brenner

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  1. Liana F. Lareau
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  2. Angela N. Brooks
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  3. David A. W. Soergel
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  4. Qi Meng
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  5. Steven E. Brenner
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  1. Banting and Best Department of Medical Research and Department of Molecular and Medical Genetics, Terrence Donnelly Center for Cellular and Biomedical Research, University of Toronto, Toronto, Canada

    Benjamin J. Blencowe Ph.D.

  2. Department of Genetics and Development Biology, University of Connecticut Health Center, Farmington, Connecticut, USA

    Brenton R. Graveley Ph.D.

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Lareau, L.F., Brooks, A.N., Soergel, D.A.W., Meng, Q., Brenner, S.E. (2007). The Coupling of Alternative Splicing and Nonsense-Mediated mRNA Decay. In: Blencowe, B.J., Graveley, B.R. (eds) Alternative Splicing in the Postgenomic Era. Advances in Experimental Medicine and Biology, vol 623. Springer, New York, NY. https://doi.org/10.1007/978-0-387-77374-2_12

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  • DOI: https://doi.org/10.1007/978-0-387-77374-2_12

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