Dr. Lynne Maquat is the J. Lowell Orbison Endowed Chair, Professor of Biochemistry & Biophysics who holds concomitant appointments in Pediatrics and in Oncology, Founding Director of the Center for RNA Biology, and Founding Chair of Graduate Women in Science at the University of Rochester, Rochester, NY. After obtaining her PhD in Biochemistry from the University of Wisconsin-Madison and undertaking post-doctoral work at the McArdle Laboratory for Cancer Research, she joined Roswell Park Cancer Institute before moving to the University of Rochester. Dr. Maquat’s research focuses on the molecular basis of human diseases, with particular interest in mechanisms of mRNA decay. Dr. Maquat discovered nonsense-mediated mRNA decay (NMD) in human diseases in 1981 and, subsequently, the exon-junction complex (EJC) and how the EJC marks mRNAs for a quality-control “pioneer” round of protein synthesis. She also discovered Staufen-mediated mRNA decay, which mechanistically competes with NMD and, by so doing, new roles for short interspersed elements and long non-coding RNAs. Additionally, she has defined a new mechanism by which microRNAs are degraded, thereby regulating mRNAs so as to promote the cell cycle. 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 received the William C. Rose Award from the American Society for Biochemistry & Molecular Biology (2014), a Canada Gairdner International Award (2015), the international RNA Society Lifetime Achievement Award in Service (2010) and in Science (2017), the FASEB Excellence in Science Award (2018), the Vanderbilt Prize in Biomedical Science (2017), the Wiley Prize in Biomedical Sciences (2018), the International Union of Biochemistry and Molecular Biology Medal (2019), the Wolf Prize in Medicine (2021), and the Warren Alpert Foundation Prize (2021). Maquat is well-known for her efforts to promote women in science.
Research in my lab focuses on RNA decay pathways. One pathway, called nonsense-mediated mRNA decay (NMD) or mRNA surveillance, surveys all newly synthesized mRNAs during what we call a "pioneer" round of translation. This round of translation involves mRNA that is associated with the cap-binding heterodimer CBP80 and CBP20. It is distinct from the type of translation that supports the bulk of cellular protein synthesis and involves a different cap-binding protein, eukaryotic initiation factor (eIF) 4E. Generally, if translation terminates more than 50-55 nt upstream of an exon-exon junction that is marked by the NMD factors Upf3 or Upf3X, Upf2 and ultimately Upf1, then the mRNA will be subject to NMD. By the time CBP80 and CBP20 have been replaced by eIF4E, the Upf mark has been removed so that mRNA is largely immune to NMD.
Studies in progress will significantly advance our understanding of the mRNP proteins, translation factors and nucleases that trigger NMD. Our results will be useful when designing therapies that aim to abrogate NMD in order to abrogate the severity of nonsense-generated diseases. We are also interested in further characterizing the pioneer translation initiation complex and requirements for its remodeling to the steady-state initiation complex that involves eIF4E. Additionally, we are interested in the cycle of posttranslational modifications that typify at least some of the NMD factors, including phosphorylation of Upf1 that is mediated by the PI 3-kinase-related protein kinase Smg1.
Over the past 15 years, our discovery and subsequent work on the mechanism of Staufen (Stau)-mediated mRNA decay (SMD) has uncovered new roles for cytoplasmic long non-coding RNAs (lncRNAs) and retrotransposon-derived short interspersed elements (SINEs) in post-transcriptional gene regulation. These SINEs include human Alu elements and mouse B1, B2, B4 and ID elements. We have shown that NMD and SMD are competitive pathways in ways that contribute to cellular homeostasis and also differentiation. We continue to define new cellular roles for SINEs as sites for nucleating intermolecular base-pairing between different mRNAs, between mRNAs and lncRNAs, and between different lncRNAs. We are additionally extending our studies of inverted-repeat Alu elements (IRAlus) and how competitive binding among the many nuclear and cytoplasmic double-stranded RNA binding proteins influence nuclear and cytoplasmic IRAlus-containing RNA metabolism.
Most recently, we have discovered a new microRNA decay pathway that is mediated by Tudor-SN. This pathway, which we call TumiD, promotes G1-to-S phase transition by degrading microRNAs that degrade mRNAs encoding proteins that promote this transition. We are currently working on how TumiD is regulated.
Please visit our lab website for more information on our exciting past and ongoing research pursuits as well as opportunities available to join our group.
Warren Alpert Prize
Sponsor: Harvard Medical School
Wolf Prize in Medicine
Sponsor: Wolf Foundation, Israel
IUBMB Jubilee Award
Sponsor: International Union of Biochemistry and Molecular Biology
Wiley Prize in Biomedical Sciences
Sponsor: Wiley Foundation
FASEB Excellence in Science Award
Sponsor: Federation of American Societies for Experimental Biology
Elected to the National Academy of Medicine
Sponsor: National Academy of Medicine (NAM)
2017 Vanderbilt Prize in Biomedical Science
2017 International RNA Society Lifetime Achievement in Science Award
Sponsor: RNA Society
Canada Gairdner International Award
Sponsor: The Gairdner Foundation
Sponsor: Women's Council of the Rochester Business Alliance
William C. Rose Award
Sponsor: American Society of Biochemistry and Molecular Biology
2013 - Present
MERIT Award from the NIH GM
Batsheva de Rothschild Fellow of the Israel Academy of Sciences and Humanities
Presidential Diversity Award
Sponsor: University of Rochester
Elected to the National Academy of Sciences
Sponsor: National Academy of Sciences
RNA Society Lifetime Achievement Award in Service
Sponsor: RNA Society
Elected to the American Academy of Arts and Sciences
Sponsor: American Academy of Arts and Sciences
Elected to the American Association for the Advancement of Science
Sponsor: American Association for the Advancement of Science
Davey Memorial Award for Outstanding Cancer Research
Sponsor: Wilmot Cancer Center, URMC
RPI/RNA Award for most significant paper co-authored by a junior scientist published in RNA
Sponsor: RNA Journal
Exemplary "Woman in Government"
Sponsor: New York State Commissioner of Health
1985 - 1989
American Heart Association Established Investigatorship
Sponsor: American Heart Association
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Cable J, Heard E, Hirose T, Prasanth KV, Chen LL, Henninger JE, Quinodoz SA, Spector DL, Diermeier SD, Porman AM, Kumar D, Feinberg MW, Shen X, Unfried JP, Johnson R, Chen CK, Wilusz JE, Lempradl A, McGeary SE, Wahba L, Pyle AM, Hargrove AE, Simon MD, Marcia M, Przanowska RK, Chang HY, Jaffrey SR, Contreras LM, Chen Q, Shi J, Mendell JT, He L, Song E, Rinn JL, Lalwani MK, Kalem MC, Chuong EB, Maquat LE, Liu X. "Noncoding RNAs: biology and applications-a Keystone Symposia report." Annals of the New York Academy of Sciences.. 2021 Nov 17; Epub 2021 Nov 17.
Kurosaki T, Sakano H, Pröschel C, Wheeler J, Hewko A, Maquat LE. "NMD abnormalities during brain development in the Fmr1-knockout mouse model of fragile X syndrome." Genome biology.. 2021 Nov 16; 22(1):317. Epub 2021 Nov 16.
Kurosaki T, Imamachi N, Pröschel C, Mitsutomi S, Nagao R, Akimitsu N, Maquat LE. "Loss of the fragile X syndrome protein FMRP results in misregulation of nonsense-mediated mRNA decay." Nature cell biology.. 2021 Jan 0; 23(1):40-48. Epub 2021 Jan 08.
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