Topic: Nonsense-mediated mRNA decay in human health and disease
Speaker: Professor Lynne Elizabeth Maquat, Department of Biochemistry and Biophysics, University of Rochester Medical Center (URMC), Wolf Prize Winner
Date and time: 10:00–12:00, November 10
Venue: Auditorium, L Building
Host: LIU Rujuan
Much progress has been made on how nonsense-mediated mRNA decay (NMD), which we first described for humans in 1981, controls the quality of gene expression by detecting and rapidly degrading aberrant mRNAs that harbor a premature termination codon. Our studies of NMD have led to the discovery of unanticipated connections between nuclear and cytoplasmic RNA metabolism, including the pioneer round of translation, and the post-splicing “mark” that is deposited on newly synthesized mRNAs, which we later named the exon-junction complex (EJC). We have also described the molecular mechanism for how NMD targets are discriminated from other cellular transcripts: the central NMD factor—the ATP-dependent RNA helicase UPF1—preferentially associates with NMD targets by virtue of a 3’-untranslated region (3’-UTR) EJC or a 3’-UTR sequence and/or structure. Importantly, NMD degrades the many mRNAs that we routinely make by mistakes in splicing or 3’-end formation. NMD also degrades ~5–10% physiologic mRNAs that are key to the maintenance of cellular homeostasis in a changing environmental milieu. NMD can be misregulated in diseases. As an example, I will present the mechanism by which Fragile X Syndrome (FXS)—a leading cause of intellectual disability and autism due to a deficiency in the RNA-binding protein Fragile X Protein (FMRP)—manifests global hyperactivation of NMD in FXS patient-derived cells and a mouse model of FXS. Possible therapeutic approaches will be discussed.
Lynne Elizabeth Maquat is the J. Lowell Orbison Endowed Chair and a professor of biochemistry and biophysics at the University of Rochester, where she is also the founding director of the Center for RNA Biology and the founding chair of Graduate Women in Science.
Prof. Maquat is an elected Fellow of the American Association for the Advancement of Science (2006); an elected Member of the American Academy of Arts & Sciences (2006), the National Academy of Sciences (2011), and the National Academy of Medicine (2017); and a Batsheva de Rothschild Fellow of the Israel Academy of Sciences & Humanities (2012-3).
She has won many scientific awards, such as the Wolf Prize in Medicine from Israel (2021), the Warren Alpert Foundation Prize from Harvard Medical School (2021), and the Gruber Genetics Prize from the Gruber Foundation and Yale University (2023).
B.S. in University of Connecticut
Ph.D. in University of Wisconsin–MadisonPostdoc. in McArdle Laboratory for Cancer Research