Specificity Determinants of the RNA Processing Exosome

University Of Rochester, Rochester NY

Investigators

Abstract

The long-term goal of these studies is a clear understanding of the molecular mechanisms that ensure the proper expression of genetic information in the form of messenger RNAs (mRNAs) in eukaryotic cells. The experiments focus on a nuclear mRNA surveillance pathway in cells that destroys aberrant mRNAs before they cause toxic effects on cell growth. Central to this pathway is a conserved complex of proteins called the exosome, which degrades mRNA molecules that fail to undergo critical steps during their formation. A major unanswered question addressed by this research is how this complex distinguishes between normal and aberrant mRNAs. Previous studies identified Rrp6p, a nuclear exoribonuclease component of the exosome and showed that it plays a critical role in degrading aberrant mRNAs in the nucleus. Recent evidence indicates that a second complex called TRAMP plays a key role in activating mRNA substrates for degradation by the nuclear exosome. Experiments described here aim to (i) identify the components of the TRAMP complex required for enhancement of Rrp6p activity, (ii) elucidate the role that TRAMP and Rrp6p play in a general and a specific pathway for mRNA degradation. These studies should shed light on the mechanisms that cells use to recognize and destroy potentially toxic RNA molecules, a process essential for the survival of all organisms. These studies will provide training for graduate and undergraduate students, including women and minorities. These studies will also generate novel cell lines that will be made available to the general scientific community for experimentation.