Structural features in the Rous sarcoma virus RNA stability element are necessary for sensing the correct termination codon

Johanna B Withers,Karen L Beemon

doi:10.1186/1742-4690-7-65

Abstract

BackgroundNonsense-mediated mRNA decay (NMD) is an mRNA quality control mechanism that selectively recognizes and targets for degradation mRNAs containing premature termination codons. Retroviral full-length RNA is presented to the host translation machinery with characteristics rarely observed among host cell mRNAs: a long 3' UTR, retained introns, and multiple open reading frames. As a result, the viral RNA is predicted to be recognized by the host NMD machinery and degraded. In the case of the Rous sarcoma virus (RSV), we identified a stability element (RSE), which resides immediately downstream of the gag termination codon and facilitates NMD evasion.ResultsWe defined key RNA features of the RSE through directed mutagenesis of the virus. These data suggest that the minimal RSE is 155 nucleotides (nts) and functions independently of the nucleotide sequence of the stop codon or the first nucleotide following the stop codon. Further data suggested that the 3'UTRs of the RSV pol and src may also function as stability elements.ConclusionsWe propose that these stability elements in RSV may be acting as NMD insulators to mask the preceding stop codon from the NMD machinery.

Highlights

Nonsense-mediated mRNA decay (NMD) is an mRNA quality control mechanism that selectively recognizes and targets for degradation mRNAs containing premature termination codons
We found that the 3′ untranslated region (UTR) of pol and src were able to substitute for the Rous sarcoma virus stability element (RSE) after the gag termination codon, while the negative control antisense RSE and the env 3′ UTR could not (Figure 6B)
We have demonstrated that Rous sarcoma virus (RSV) has RNA stability elements immediately downstream of the open reading frames of gag, pol, and src

Summary

Introduction

Nonsense-mediated mRNA decay (NMD) is an mRNA quality control mechanism that selectively recognizes and targets for degradation mRNAs containing premature termination codons. Nonsense-mediated mRNA decay (NMD) selectively recognizes and targets for degradation mRNAs containing premature termination codons. This mRNA quality control mechanism prevents potentially deleterious dominant negative effects of truncated proteins that accumulate if aberrant mRNAs are not degraded [1,2,3,4]. NMD proteins can efficiently identify a termination codon as premature if the stop codon resides at least 50 nucleotides upstream of the terminal exon-exon junction [5,6].

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Conclusion