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Intranuclear degradation of nonsense codon‐containing mRNA

Marc Bühler, Miles F Wilkinson, Oliver Mühlemann

Author Affiliations

  1. Marc Bühler1,
  2. Miles F Wilkinson2 and
  3. Oliver Mühlemann*,1
  1. 1 Institute of Cell Biology, University of Bern, Baltzerstrasse 4, CH‐3012, Bern, Switzerland
  2. 2 Department of Immunology, University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030, USA
  1. *Corresponding author. Tel: +41 31 631 4627; Fax: +41 31 631 4616; E-mail: oliver.muehlemann{at}izb.unibe.ch
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Abstract

Most vertebrate mRNAs with premature termination codons (PTCs) are specifically recognized and degraded by a process referred to as nonsense‐mediated mRNA decay (NMD) while still associated with the nucleus. However, it is still a matter of debate whether PTCs can be identified by intranuclear scanning or only by ribosomes on the cytoplasmic side of the nuclear envelope. Here we show that inhibition of mRNA export by two independent approaches does not affect the downregulation of PTC‐containing T‐cell receptor β transcripts in the nuclear fraction of mammalian cells, providing strong evidence for intranuclear NMD. Our results are fully consistent with recently reported evidence for nuclear translation and suggest that an important biological role for nuclear ribosomes is the early elimination of nonsense mRNA during a pioneer round of translation.

  • Received March 11, 2002.
  • Revision received May 10, 2002.
  • Accepted May 16, 2002.
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