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Upf1 and Upf2 proteins mediate normal yeast mRNA degradation when translation initiation is limited
1Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia B3H 4H7, Canada. cabarnes@is.dal.ca
Abstract:
mRNA degradation is coupled with the process of mRNA translation. For example, an mRNA molecule, on which translation is prematurely terminated because of a nonsense codon, may be rapidly degraded. This nonsense-mediated mRNA decay in the yeast Saccharomyces cerevisiae is mediated by the Upf1 and Upf2 proteins. Yeast mRNAs can also be selectively destabilized by limiting the rate of translation initiation. Two such destabilized mRNAs, from the SSA1 and SSA2 genes, have been identified using temperature-sensitive mutations affecting the Prt1 component of eukaryotic initiation factor 3. For SSA1 and SSA2 mRNAs, and for structurally modified SSA mRNA derivatives, I show here that degradation is triggered when translation initiation is limited but ongoing. This initiation-dependent mRNA degradation is limited to a subset of mRNAs that includes at least those from the SSA1 and SSA2 genes, and occurs through Upf1- and Upf2-mediated processes, although sequence elements characteristic of nonsense-mediated decay are not evident in these mRNAs.
Insights
mRNA degradation is linked to translation. Limited translation initiation triggers degradation of specific mRNAs, like SSA1 and SSA2, via Upf1 and Upf2 proteins in yeast.
Area of Science:
- Molecular Biology
- Yeast Genetics
- Gene Regulation
Background:
- mRNA degradation is intrinsically linked to mRNA translation.
- Nonsense-mediated mRNA decay (NMD) in yeast (Saccharomyces cerevisiae) is a known pathway involving Upf1 and Upf2 proteins, degrading mRNAs with premature termination codons.
- Specific yeast mRNAs can be destabilized by limiting translation initiation rates.
Purpose of the Study:
- To investigate the mechanism of mRNA degradation triggered by limited translation initiation.
- To identify specific mRNAs affected by impaired translation initiation.
- To determine the protein factors involved in this degradation pathway.
Main Methods:
- Utilized temperature-sensitive mutations in the Prt1 component of eukaryotic initiation factor 3 to limit translation initiation.
- Analyzed the degradation rates of SSA1 and SSA2 mRNAs and their derivatives under conditions of limited initiation.
- Investigated the role of Upf1 and Upf2 proteins in initiation-dependent mRNA degradation.
Main Results:
- Demonstrated that degradation of SSA1 and SSA2 mRNAs is triggered when translation initiation is limited but ongoing.
- Identified that this initiation-dependent mRNA degradation affects a specific subset of mRNAs, including SSA1 and SSA2.
- Showed that the Upf1 and Upf2 protein-mediated pathway is involved, despite the absence of typical nonsense-mediated decay sequence elements.
Conclusions:
- Limited translation initiation can actively trigger mRNA degradation in yeast.
- This process, distinct from canonical NMD, involves Upf1 and Upf2 proteins and targets specific mRNAs like SSA1 and SSA2.
- The findings reveal a novel layer of gene regulation through translation initiation-dependent mRNA decay.