mRNA Degradation and Quality Control of
Gene Expression in Eukaryotes

Gene expression is a complex process that all life forms need to carry out in a precisely controlled fashion. The degradation of mRNA serves important roles in this process. For example degradation rates of individual mRNAs can be regulated and affect mRNA abundance, and thus how much of each protein is produced by translation. mRNA decay also plays an important role in maintaining the overall fidelity of gene expression by preferentially degrading aberrant mRNAs that are made by mistakes during mRNA processing reactions. One example of aberrant mRNAs that are extremely rapidly degraded are those that lack a stop codon. Such "nonstop" mRNAs are produced frequently by premature addition of a poly(A) tail.

The yeast Saccharomyces cerevisiae and probably most other eukaryotes have two general pathways to degrade mRNA. These two pathways both degrade stable and unstable mRNAs. Thus, the key to understanding differential mRNA degradation is to understand the interactions of a particular mRNA with the basal machinery.

One of the two pathways of mRNA degradation is carried out by the exosome. The exosome is a complex containing multiple 3' to 5' exonucleases that not only degrades mRNA, but also functions in the maturation of many RNAs from 3' extended precursors. This raises interesting questions such as why there are so many RNases in one complex, and how does the exosome completely degrade some RNAs, but process others.

Research in my lab is focused on understanding in molecular detail how a particular mRNA interacts with the mRNA decay machinery and how this causes its degradation. The rapid recognition and degradation of nonstop mRNAs serve as a useful model in these experiments.