Graduate Research Assistant

Biochemistry and Molecular Biology

Cancer Center

University of Maryland, Baltimore (Baltimore, MD)

Dr. Eric Toth

The focus of my work is the biochemical characterization of the Saccaromyces Cerevisae Mtr4p RNA helicase.

Accurate processing of precursor RNA and timely degradation of aberrant RNAs is crucial for proper cell function. Ribosomal, small nuclear and small nucleolar RNAs are all initially synthesized as long precursors, which must then be trimmed to form functional RNAs[1]. Any byproducts of this trimming as well as any defective RNAs must be rapidly degraded. These processing events are mediated by the 3′5′ single stranded exonucleolytic RNA degradation machinery consisting of an exonuclease complex called the exosome and the helicase Mtr4p. Mtr4p is a critical partner of the exosome that presumably maintains the momentum of exonucleolytic decay/processing by removing secondary structures of the target RNAs. We have shown that Mtr4p is in fact a bona fide helicase with 3′5′ polarity and that this activity is dependent on hydrolysis of (d)ATP. Our studies also examined the RNA binding parameters of Mtr4p showing that Mtr4p binds single stranded RNA in a length and nucleotide-dependent manner. These studies also showed that Mtr4p has a unique interaction with polyA RNA substrates. Taken together, these studies offer an initial characterization of the essential activities of Saccharomyces cerevisiae Mtr4p and provide insight into how it might function within the context of the nuclear exosome.