A Small Segment of the MATα1 Transcript Promotes mRNA Decay in Saccharomyces cerevisiae: a Stimulatory Role for Rare Codons

Abstract

Differences in decay rates of eukaryotic transcripts can be determined by discrete sequence elements within mRNAs. Through the analysis of chimeric transcripts and internal deletions, we have identified a 65-nucleotide segment of the MATα1 mRNA coding region, termed the MATα1 instability element, that is sufficient to confer instability to a stable PGK1 reporter transcript and that accelerates turnover of the unstable MATα1 mRNA. This 65-nucleotide element is composed of two parts, one located within the 5' 33 nucleotides and the second located in the 3' 32 nucleotides. The first part, which can be functionally replaced by sequences containing rare codons, is unable to promote rapid decay by itself but can enhance the action of the 3' 32 nucleotides (positions 234 to 266 in the MATα1 mRNA) in accelerating turnover. A second portion of the MATα1 mRNA (nucleotides 265 to 290) is also sufficient to destabilize the PGK1 reporter transcript when positioned 3' of rare codons, suggesting that the 3' half of the MATα1 instability element is functionally reiterated within the MATα1 mRNA. The observation that rare codons are part of the 65-nucleotide MATα1 instability element suggests possible mechanisms through which translation and mRNA decay may be linked.