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Published online 3 February 2004

Nucleic Acids Research, 2004, Vol. 32, No. 2 784-790
© 2004 Oxford University Press

A programmed –1 ribosomal frameshift signal can function as a cis-acting mRNA destabilizing element

Ewan P. Plant, Pinger Wang1, Jonathan L. Jacobs and Jonathan D. Dinman*

Department of Cell Biology and Molecular Genetics, Microbiology Building Room 2135, University of Maryland, College Park, MD 20742, USA and 1 Centocor, Pharmaceutical Sciences, Analytical OCD Building Room B-26, 1001 Route 202N, Raritan, NJ 08869, USA

*To whom correspondence should be addressed. Tel: +1 301 405 0981; Fax: +1 301 314 9489; Email: dinman{at}umd.edu

Nonsense-mediated mRNA decay (NMD) directs rapid degradation of premature termination codon (PTC)-containing mRNAs, e.g. those containing frameshift mutations. Many viral mRNAs encode polycistronic messages where programmed –1 ribosomal frameshift (–1 PRF) signals direct ribosomes to synthesize polyproteins. A previous study, which identified consensus –1 PRF signals in the yeast genome, found that, in contrast to viruses, the majority of predicted –1 PRF events would direct translating ribosomes to PTCs. Here we tested the hypothesis that a –1 PRF signal can function as a cis-acting mRNA destabilizing element by inserting an L-A viral –1 PRF signal into a PGK1 reporter construct in the ‘genomic’ orientation. The results show that even low levels of –1 PRF are sufficient to target the reporter mRNA for degradation via the NMD pathway, with half-lives similar to messages containing in-frame PTCs. The demonstration of an inverse correlation between frameshift efficiency and mRNA half-lives suggests that modulation of –1 PRF frequencies can be used to post-transcriptionally regulate gene expression. Analysis of the mRNA decay profiles of the frameshift-signal- containing reporter mRNAs also supports the notion that NMD remains active on mRNAs beyond the ‘pioneer round’ of translation in yeast.


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