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Widespread predicted nonsense-mediated mRNA decay of alternatively-spliced transcripts of human normal and disease

Richard E Green1, Benjamin P Lewis, R Tyler Hillman

  • 1Department of Plant and Microbial Biology, University of California, Berkeley, CA 94720, USA.

Bioinformatics (Oxford, England)
|July 12, 2003
PubMed

Insights

A third of alternative mRNA transcripts may be degraded by nonsense-mediated mRNA decay (NMD), a cellular surveillance system. This process could play a significant role in various human diseases.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cellular Biology

Background:

  • Nonsense-mediated mRNA decay (NMD) is a crucial mRNA surveillance pathway that eliminates aberrant transcripts.
  • Alternative mRNA splicing generates diverse transcript variants, some of which may be targeted by NMD.

Purpose of the Study:

  • To investigate the prevalence of NMD targets among reliably-inferred alternative mRNA isoforms.
  • To explore the potential role of NMD in human diseases.

Main Methods:

  • Analysis of reliably-inferred alternative mRNA isoforms.
  • Experimental studies to validate NMD targeting and its consequences.

Main Results:

  • Approximately one-third of alternative mRNA isoforms are predicted to be NMD candidates.
  • Initial experimental data support the degradation of these NMD-targeted transcripts.
  • Evidence suggests a potential role for NMD in the pathogenesis of human diseases.

Conclusions:

  • A substantial fraction of alternative mRNA isoforms are subject to NMD.
  • NMD may represent an underappreciated factor in the development of human diseases.
  • Further research is warranted to elucidate the specific roles of NMD in disease.

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