Associate Professor of Biology at Williams since 1994
Associate Dean for Institutional Diversity
Director, Howard Hughes Medical Institute Science Education Program
Office: 226 BSC
Lab: 236 BSC
Phone: (413) 597-3536
Area of Interest: Molecular Genetics
Biochemical components of tRNA stability
Post-transcriptional modifications of transfer RNA (tRNA) guarantee tRNA’s stability and function. These extensive and varied chemical changes require a whole host of highly conserved enzymes. One of these enzymes, pseudouridine synthase 4 (Pus4), catalyzes the conversion of uridine to psuedouridine at position 55; this modification occurs in almost every tRNA tested from archaebacteria, eubacteria, and eukaryotes.
Despite this apparent near universality of Pus4’s function, deletion of PUS4 in Saccharomyces cerevisiae (or deletion of its ortholog TruB in E. coli) causes no obvious consequences for cellular viability. We have thus employed synthetic genetic array (SGA) analysis (Tong et al. (2001) Science 294, 2364-2368) to identify deletion mutations that exhibit lethal and sick interactions with a pus4 deletion. Our goal is to find a molecular explanation for the seeming disparity between the extreme conservation of PUS4 and its apparent dispensability. David Arnolds ’04 and Anna Brosius ’05, two previous thesis students, discovered synthetic lethal/sick interactions that suggest that other tRNA-modifying enzymes apparently back up Pus4’s function by adding layers of stability to tRNA. Fascinatingly, the network of interacting chemistries identified by these studies suggests unforeseen chemical interactions within the tRNA molecule. Future research will use genetic, biochemical, and cytological approaches to characterize these interactions.