In eukaryotic cells, the decay rates of individual mRNAs can vary by more than an order of magnitude. These differences can have profound effects on the level of gene expression and can also serve as important sites for post-transcriptional gene regulation. Despite this significance, little is known about the mechanisms of the decay process or the features of individual mRNAs which dictate their respective decay rates. The focus of our laboratory is to understand the mechanisms and regulation of mRNA turnover, utilizing the powerful molecular genetic techniques available in Saccharomyces cerevisiae.

We have described a mechanism of mRNA decay in yeast in which poly(A) tail shortening triggers a nucleolytic cleavage at, or near, the cap structure, leading to 5' to 3' exonucleolytic degradation of the transcript. Since this decay pathway involves structures found on essentially all mRNAs, the poly(A) tail and the cap, this may be a general mechanism for the decay of many eukaryotic transcripts. Current goals in the lab are to determine the spectrum of mRNAs degraded by this decay mechanism, to identify the gene products that perform and regulate the nucleolytic steps in mRNA decay, and to identify the molecular mechanisms by which cis-acting sequences that regulate mRNA decay influence the rates of poly(A) tail shortening and decapping.