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

@article{citeulike:2604914, abstract = {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. 10.1093/nar/gkh256}, author = {Plant, Ewan P. and Wang, Pinger and Jacobs, Jonathan L. and Dinman, Jonathan D.}, citeulike-article-id = {2604914}, citeulike-linkout-0 = {http://dx.doi.org/10.1093/nar/gkh256}, citeulike-linkout-1 = {http://nar.oxfordjournals.org/cgi/content/abstract/32/2/784}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/14762205}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=14762205}, day = {3}, doi = {10.1093/nar/gkh256}, journal = {Nucl. Acids Res.}, keywords = {codon, consensus, frameshift, genes, genomics, hypothesis, mrna, mutation, nmd, polycistronic, ribosome, transcription, translation, virus, yeast}, month = {February}, number = {2}, pages = {784--790}, posted-at = {2008-03-28 04:22:52}, priority = {0}, title = {A programmed -1 ribosomal frameshift signal can function as a cis-acting mRNA destabilizing element}, url = {http://dx.doi.org/10.1093/nar/gkh256}, volume = {32}, year = {2004} }

TY - JOUR ID - citeulike:2604914 L3 - citeulike-article-id:2604914 N2 - 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. 10.1093/nar/gkh256 IS - 2 JF - Nucl. Acids Res. EP - 790 TI - A programmed -1 ribosomal frameshift signal can function as a cis-acting mRNA destabilizing element VL - 32 SP - 784 KW - codon KW - consensus KW - frameshift KW - genes KW - genomics KW - hypothesis KW - mrna KW - mutation KW - nmd KW - polycistronic KW - ribosome KW - transcription KW - translation KW - virus KW - yeast AU - Plant, Ewan AU - Wang, Pinger AU - Jacobs, Jonathan AU - Dinman, Jonathan PY - 2004/02/03/ UR - http://dx.doi.org/10.1093/nar/gkh256 ER -