A SMALL SEGMENT OF THE MAT-ALPHA-1 TRANSCRIPT PROMOTES MESSENGER-RNA DECAY IN SACCHAROMYCES-CEREVISIAE - A STIMULATORY ROLE FOR RARE CODONS

Differences in decay rates of eukaryotic transcripts can be determined by discrete sequence elements within mRNAs. Through the analysis of c himeric transcripts and internal deletions, we have identified a 65-nu cleotide segment of the MATalpha1 mRNA coding region, termed the MATal pha1 instability element, that is sufficient to confer instability to a stable PGK1 reporter transcript and that accelerates turnover of the unstable MATalpha1 mRNA. This 65-nucleotide element is composed of tw o parts, one located within the 5' 33 nucleotides and the second locat ed in the 3' 32 nucleotides. The first part, which can be functionally replaced by sequences containing rare codons, is unable to promote ra pid decay by itself but can enhance the action of the 3' 32 nucleotide s (positions 234 to 266 in the MATalpha1 mRNA) in accelerating turnove r. A second portion of the MATalpha1 mRNA (nucleotides 265 to 290) is also sufficient to destabilize the PGK1 reporter transcript when posit ioned 3' of rare codons, suggesting that the 3' half of the MATalpha1 instability element is functionally reiterated within the MATalpha1 mR NA. The observation that rare codons are part of the 65-nucleotide MAT alpha1 instability element suggests possible mechanisms through which translation and mRNA decay may be linked.