Nucleic Acids Research Advance Access originally published online on December 7, 2006
Nucleic Acids Research 2007 35(1):165-174; doi:10.1093/nar/gkl1033
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Nucleic Acids Research, 2007, Vol. 35, No. 1 165-174
© 2006 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Genomics |
Identification of functional, endogenous programmed –1 ribosomal frameshift signals in the genome of Saccharomyces cerevisiae
Department of Cell Biology & Molecular Genetics, University of Maryland 2135 Microbiology Building, College Park, MD 20742, USA
*To whom correspondence should be addressed. Tel: +1 301 405 0918; Fax: +1 301 314 9489; Email: dinman{at}umd.edu
Received August 2, 2006. Revised September 29, 2006. Accepted November 6, 2006.
In viruses, programmed –1 ribosomal frameshifting (–1 PRF) signals direct the translation of alternative proteins from a single mRNA. Given that many basic regulatory mechanisms were first discovered in viral systems, the current study endeavored to: (i) identify –1 PRF signals in genomic databases, (ii) apply the protocol to the yeast genome and (iii) test selected candidates at the bench. Computational analyses revealed the presence of 10 340 consensus –1 PRF signals in the yeast genome. Of the 6353 yeast ORFs, 1275 contain at least one strong and statistically significant –1 PRF signal. Eight out of nine selected sequences promoted efficient levels of PRF in vivo. These findings provide a robust platform for high throughput computational and laboratory studies and demonstrate that functional –1 PRF signals are widespread in the genome of Saccharomyces cerevisiae. The data generated by this study have been deposited into a publicly available database called the PRFdb. The presence of stable mRNA pseudoknot structures in these –1 PRF signals, and the observation that the predicted outcomes of nearly all of these genomic frameshift signals would direct ribosomes to premature termination codons, suggest two possible mRNA destabilization pathways through which –1 PRF signals could post-transcriptionally regulate mRNA abundance.
Present address: Jonathan L. Jacobs, Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, Advanced Technology Center, Gaithersburg, MD 20877, USA
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