9th Annual Workshop, October 28-31, 1999
Co-sponsored by the U.S. Department of Energy
Understanding the role of mRNA turnover in regulating gene expression and in disease states
Robert Wood Johnson Medical School-UMDNJ, Piscataway, New Jersey, USA
It is now clear the regulation of mRNA decay provides a powerful means of controlling gene expression. The mechanisms and structural features that dictate mRNA decay rates, and their regulation, are now being defined. These studies have revealed that the processes of translation and mRNA turnover are intimately linked. A clear example of this link is the observation that premature translation termination enhances mRNA decay rates, a phenomena called nonsense-mediated mRNA decay (NMD). Transcripts containing premature nonsense codons are rapidly degraded, thus preventing synthesis of incomplete and potentially deleterious proteins. There are well over two hundred genetic disorders which can result from premature translation termination. Understanding how this process affects translation termination and mRNA degradation can lead to rational approaches for the treatment of these disorders. We have been characterizing the sequence and factors involved in NMD. These results have identified a "surveillance complex" that monitors the translation process and determines whether translation termination has occurred at the correct position within the mRNA. These results have led to a model that in which the surveillance complex assesses translation termination by monitoring the transition of an RNP as it is converted from a nuclear to a cytoplasmic form during the initial rounds of translation.