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A programmed -1 ribosomal frameshift signal can function as a cis-acting mRNA destabilizing element.
Ewan P Plant1, Pinger Wang, Jonathan L Jacobs
1Department of Cell Biology and Molecular Genetics, Microbiology Building Room 2135, University of Maryland, College Park, MD 20742, USA.
Nucleic Acids Research
|February 6, 2004
Summary
Programmed ribosomal frameshifting signals can destabilize mRNA. In yeast, these signals trigger nonsense-mediated mRNA decay (NMD), similar to premature stop codons, offering a new gene regulation mechanism.
Area of Science:
- Molecular Biology
- Genetics
- RNA Biology
Background:
- Nonsense-mediated mRNA decay (NMD) degrades mRNAs with premature termination codons (PTCs).
- Programmed -1 ribosomal frameshifting (-1 PRF) is common in viral polycistronic mRNAs but less understood in yeast.
- Previous studies suggest yeast -1 PRF signals may lead to PTCs.
Purpose of the Study:
- To investigate if -1 PRF signals act as cis-acting mRNA destabilizing elements in yeast.
- To determine if -1 PRF targets mRNAs for degradation via the NMD pathway.
Main Methods:
- Insertion of an L-A viral -1 PRF signal into a PGK1 reporter construct in yeast.
- Analysis of reporter mRNA half-lives and decay profiles.
- Correlation analysis between frameshift efficiency and mRNA stability.
Main Results:
- Even low levels of -1 PRF efficiently targeted reporter mRNA for degradation by NMD.
- Reporter mRNA half-lives were comparable to those with in-frame PTCs.
- An inverse correlation was observed between frameshift efficiency and mRNA half-life.
- NMD activity was confirmed on mRNAs beyond the initial translation round.
Conclusions:
- -1 PRF signals can function as potent mRNA destabilizing elements in yeast.
- NMD pathway degrades mRNAs containing -1 PRF signals.
- Modulating -1 PRF frequency offers a mechanism for post-transcriptional gene regulation.
- NMD remains active on mRNAs throughout translation in yeast.