Abstract
Author SummaryCellular 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.
Highlights
MRNA degradation controls the level of gene expression and ensures transcript quality control
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
Summary
MRNA degradation controls the level of gene expression and ensures transcript quality control. In the yeast Saccharomyces cerevisiae, most wild-type mRNAs are degraded by the general 59 to 39 or 39 to 59 decay pathways [1]. Transcript-specific decay pathways have been identified in several experimental systems [6,7]. In each of these pathways, degradation of a transcript is regulated by specific cis-acting elements and their respective trans-regulatory RNA-binding factors. Those of Badis et al, have identified a yeast cytoplasmic, transcript-specific decay pathway, mediated by the decapping activator Edc3p, that principally targets only two transcripts, RPS28B mRNA and intron-containing YRA1 premRNA [14,15]
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