This seminar has been cancelled. It will be rescheduled at a later date. [New date/time will be Wednesday, March 29 from 1:00-2:00 pm.]
*** NOTE: Time & Date is Monday, March 20th from 2:00-3:00 PM ***
ABSTRACT: My research examines how protein synthesis concludes on normal and defective mRNAs. Understanding how these processes are choregraphed is crucial for human health; for example, 11% of all heritable human diseases are caused by premature stop codons. As a postdoctoral fellow, I defined the molecular events that liberate polypeptides from ribosomes as translation concludes on normal mRNAs. Using an in vitro reconstituted yeast translation system and single-molecule assays, I tracked the interplay of eukaryotic release factors (eRF1 and eRF3) with ribosomes halted at stop codons. I discovered that eRF1 and eRF3 act together to quickly recognize stop codons and elicit termination via a tightly regulated process that resembles how ribosomes select proper tRNAs in translation elongation, which explains how translation termination is fast yet also specific for stop codons. Since the release factors are well conserved throughout eukaryotes, these mechanisms are likely a fundamental feature of eukaryotic protein synthesis. My work also revealed that diverse effectors inhibit translation termination to promote stop codon readthrough, suggesting a new route to treat diseases caused by premature stop codons which includes cystic fibrosis and hereditary cancers. In the future, I will use single-molecule and structural approaches to watch translation unfold on defective mRNAs to understand the molecular events used to evaluate mRNAs and prevent the repeated synthesis of toxic proteins.