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Science 22 March 2002:
Vol. 295. no. 5563, pp. 2262 - 2264
DOI: 10.1126/science.1067272
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Reports

Exosome-Mediated Recognition and Degradation of mRNAs Lacking a Termination Codon

Ambro van Hoof,12* Pamela A. Frischmeyer,13 Harry C. Dietz,13 Roy Parker12*

One role of messenger RNA (mRNA) degradation is to maintain the fidelity of gene expression by degrading aberrant transcripts. Recent results show that mRNAs without translation termination codons are unstable in eukaryotic cells. We used yeast mutants to demonstrate that these "nonstop" mRNAs are degraded by the exosome in a 3'-to-5' direction. The degradation of nonstop transcripts requires the exosome-associated protein Ski7p. Ski7p is closely related to the translation elongation factor EF1A and the translation termination factor eRF3. This suggests that the recognition of nonstop mRNAs involves the binding of Ski7p to an empty aminoacyl-(RNA-binding) site (A site) on the ribosome, thereby bringing the exosome to a mRNA with a ribosome stalled near the 3' end. This system efficiently degrades mRNAs that are prematurely polyadenylated within the coding region and prevents their expression.

1 Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD 20815, USA.
2 University of Arizona, Department of Molecular and Cellular Biology, Tucson, AZ 85721, USA.
3 Johns Hopkins University, Institute for Genetic Medicine, School of Medicine, Baltimore, MD 21205, USA.
*   To whom correspondence should be addressed. E-mail: ambro{at}u.arizona.edu (A.v.H.) or rrparker{at}u.arizona.edu (R.P.)

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Science. ISSN 0036-8075 (print), 1095-9203 (online)