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J. Biol. Chem., Vol. 279, Issue 12, 11081-11087, March 19, 2004

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Factors That Influence Selection of Coding Resumption Sites in Translational Bypassing

MINIMAL CONVENTIONAL PEPTIDYL-tRNA:mRNA PAIRING CAN SUFFICE^*

Alan J. Herr, Norma M. Wills, Chad C. Nelson, Raymond F. Gesteland, and John F. Atkins¶

From the Department of Human Genetics, University of Utah, Salt Lake City, Utah 84112-5330

This study investigates bypassing initiated from codons immediately 5' of a stop codon. The mRNA slips and is scanned by the peptidyl-tRNA for a suitable landing site, and standard decoding resumes at the next 3' codon. This work shows that landing sites with potentially strong base pairing between the peptidyl-tRNA anticodon and mRNA are preferred, but sites with little or no potential for Watson-Crick or wobble base pairing can also be utilized. These results have implications for re-pairing in ribosomal frameshifting. Shine-Dalgarno sequences in the mRNA can alter the distribution of landing sites observed. The bacteriophage T4 gene 60 nascent peptide, known to influence take-off in its native context, imposes stringent P-site pairing requirements, thereby limiting the number of suitable landing sites.

Received for publication, October 20, 2003 , and in revised form, December 10, 2003.

^* This work was supported in part by National Institutes of Health Grant GM48152 (to J. F. A.) and Department of Energy Grant FG03-01ER63132 (to R. F. G.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains Figs. 1–4.

Both authors contributed equally to this work and should be considered as joint first authors.

Supported by National Institutes of Health Genetics Training Grant 5T32GM07464-24. Present address: Sainsbury Laboratory, John Innes Centre, Norwich, NR4 7UH, United Kingdom.

^¶ To whom correspondence should be addressed: Dept. of Human Genetics, University of Utah, 15 N. 2030 E., Salt Lake City, UT 84112-5330. Tel.: 801-585-3434; Fax: 801-585-3910; E-mail: john.atkins{at}genetics.utah.edu.

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