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Degradation of YRA1 Pre-mRNA in the Cytoplasm Requires Translational Repression, Multiple Modular Intronic Elements, Edc3p, and Mex67p
Degradation of YRA1 Pre-mRNA in the Cytoplasm Requires Translational Repression, Multiple Modular Intronic Elements, Edc3p, and Mex67p
- Source :
- PLoS Biology, PLoS Biology, Vol 14, Iss 5, p e1002470 (2016)
- Publication Year :
- 2016
-
Abstract
- The yeast YRA1 pre-mRNA contains multiple intronic elements that regulate transcript decay and translatability via the Edc3p decapping activator and the Mex67p/Mtr2p export receptor.<br />Intron-containing pre-mRNAs are normally retained and processed in the nucleus but are sometimes exported to the cytoplasm and degraded by the nonsense-mediated mRNA decay (NMD) pathway as a consequence of their inclusion of intronic in-frame termination codons. When shunted to the cytoplasm by autoregulated nuclear export, the intron-containing yeast YRA1 pre-mRNA evades NMD and is targeted by a cytoplasmic decay pathway mediated by the decapping activator Edc3p. Here, we have elucidated this transcript-specific decay mechanism, showing that Edc3p-mediated YRA1 pre-mRNA degradation occurs independently of translation and is controlled through five structurally distinct but functionally interdependent modular elements in the YRA1 intron. Two of these elements target the pre-mRNA as an Edc3p substrate and the other three mediate transcript-specific translational repression. Translational repression of YRA1 pre-mRNA also requires the heterodimeric Mex67p/Mtr2p general mRNA export receptor, but not Edc3p, and serves to enhance Edc3p substrate specificity by inhibiting the susceptibility of this pre-mRNA to NMD. Collectively, our data indicate that YRA1 pre-mRNA degradation is a highly regulated process that proceeds through translational repression, substrate recognition by Edc3p, recruitment of the Dcp1p/Dcp2p decapping enzyme, and activation of decapping.<br />Author Summary Cellular mRNA levels are governed by competing rates of synthesis and decay. At the same time, mRNA decay pathways prevent the expression of defective mRNAs. The molecular mechanisms underlying the regulation of mRNA decay in eukaryotic cells are not well understood. We investigated a yeast transcript-specific decay pathway that targets the intron containing pre-mRNA for the mRNA export factor Yra1p when this pre-mRNA is shunted to the cytoplasm by autoregulated nuclear export. Our experiments demonstrate that the Edc3p decapping activator mediates YRA1 pre-mRNA decay and that this process is independent of translation. Instead, it is controlled through five functionally interdependent modular elements contained in the YRA1 intron. Whereas two of these elements confer Edc3p substrate specificity, the other three mediate translational repression of the YRA1 pre-mRNA. Additionally, we found that translational repression of YRA1 pre-mRNA requires Mex67p/Mtr2p, an mRNA export receptor, and enhances Edc3p substrate specificity by inhibiting the susceptibility of this pre-mRNA to nonsense-mediated mRNA decay. Our data highlight the intrinsic interconnections between different steps in gene expression and suggest that mRNA export factors in general may have important roles in controlling cytoplasmic mRNA translation and decay.
- Subjects :
- Cytoplasm
Nucleocytoplasmic Transport Proteins
Saccharomyces cerevisiae Proteins
QH301-705.5
RNA Stability
Recombinant Fusion Proteins
Saccharomyces cerevisiae
General Biochemistry, Genetics and Molecular Biology
Gene Expression Regulation, Fungal
Molecular Biology/Translational Regulation
Endoribonucleases
RNA Precursors
Biology (General)
General Immunology and Microbiology
General Neuroscience
Correction
Membrane Transport Proteins
Nuclear Proteins
RNA-Binding Proteins
Genetics and Genomics/Gene Expression
Introns
Genetics and Genomics/Gene Function
RNA Cap-Binding Proteins
Protein Biosynthesis
Molecular Biology/mRNA Stability
General Agricultural and Biological Sciences
Research Article
Subjects
Details
- ISSN :
- 15457885
- Volume :
- 14
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- PLoS biology
- Accession number :
- edsair.doi.dedup.....2e3ca91e4422b7fd549c779a7933a395