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Special Biochemistry Seminar – Michael Lawson

Biochemistry, Special Seminars

January 9, 2023 11:00 am - 12:00 pm
Mani L. Bhaumik Centennial Collaboratory
607 Charles E. Young Dr., East
Los Angeles, CA 90095 United States
Speaker Michael Lawson


Michael Lawson Seminar

Title: Defining the Pathways of Eukaryotic Translational Quality Control

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.

Michael Lawson

Biochemistry, Special Seminars

Department of Structural Biology,
Stanford University School of Medicine