Key result
Insertion of a -1 ribosomal frameshift signal into a reporter construct targeted the mRNA for degradation via the nonsense-mediated decay pathway, with half-lives similar to messages with in-frame PTCs.
A -1 PRF signal can function as a cis-acting mRNA destabilizing element, suggesting that modulation of -1 PRF frequencies can post-transcriptionally regulate gene expression.
No immediate clinical implications; leaves open whether -1 PRF modulation regulates endogenous gene expression in vivo.
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.
No takes yet. Share an insight, caveat, or question.
Ewan P. Plant (2004) studied this question. Insertion of an L-A viral -1 PRF signal into a PGK1 reporter construct vs. Messages containing in-frame PTCs was evaluated on mRNA degradation via the NMD pathway and mRNA half-lives. Insertion of a -1 ribosomal frameshift signal into a reporter construct targeted the mRNA for degradation via the nonsense-mediated decay pathway, with half-lives similar to messages with in-frame PTCs.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: