[SLST Seminar] Nonsense-mediated mRNA decay in human health and disease

ON2023-11-07TAG: ShanghaiTech UniversityCATEGORY: Lecture

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–Madison

Postdoc. in McArdle Laboratory for Cancer Research