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Lynne Elizabeth Maquat, Ph.D.

Contact Information

Phone Numbers

Office: (585) 273-5640

Fax: (585) 271-2683

Research Labs

Faculty Appointments

Biography

Professional Background

Lynne Elizabeth 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 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), and the Wolf Prize in Medicine from the Wolf Foundation in Israel (2021). Maquat is well-known for her efforts to promote women in science.

Research

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.

Credentials

Education

1974
BA | University of Connecticut
Biology

1979
PhD | Univ Wisconsin-Madison
Biochemistry

Awards

2021
Wolf Prize in Medicine
Sponsor: Wolf Foundation, Israel

2019
IUBMB Jubilee Award
Sponsor: International Union of Biochemistry and Molecular Biology

2018
Wiley Prize in Biomedical Sciences
Sponsor: Wiley Foundation

2018
FASEB Excellence in Science Award
Sponsor: Federation of American Societies for Experimental Biology

2017
Elected to the National Academy of Medicine
Sponsor: National Academy of Medicine (NAM)

2017
2017 Vanderbilt Prize in Biomedical Science
Sponsor: Vanderbilt

2017
2017 International RNA Society Lifetime Achievement in Science Award
Sponsor: RNA Society

2015
Canada Gairdner International Award
Sponsor: The Gairdner Foundation

2014
Athena Award
Sponsor: Women's Council of the Rochester Business Alliance

2014
William C. Rose Award
Sponsor: American Society of Biochemistry and Molecular Biology

2013 - Present
MERIT Award from the NIH GM

2013
Batsheva de Rothschild Fellow of the Israel Academy of Sciences and Humanities

2013
Presidential Diversity Award
Sponsor: University of Rochester

2011
Elected to the National Academy of Sciences
Sponsor: National Academy of Sciences

2010
RNA Society Lifetime Achievement Award in Service
Sponsor: RNA Society

2006
Elected to the American Academy of Arts and Sciences
Sponsor: American Academy of Arts and Sciences

2006
Elected to the American Association for the Advancement of Science
Sponsor: American Association for the Advancement of Science

2002
Davey Memorial Award for Outstanding Cancer Research
Sponsor: Wilmot Cancer Center, URMC

1998
RPI/RNA Award for most significant paper co-authored by a junior scientist published in RNA
Sponsor: RNA Journal

1990
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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Patents

Patent Title: Methods and Compositions Related to Staufen 1 Binding Sites Formed By Duplexing ALU Elements
Patent #: 9,206,479
Issue Date: Dec 08, 2015
Country: United States
Invented By: Chenguang Gong, Lynne E Maquat

Publications

Journal Articles

1/2021
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.

10/5/2020
Rambout X, Maquat LE. "NCBP3: A Multifaceted Adaptive Regulator of Gene Expression." Trends in biochemical sciences.. 2020 Oct 5; Epub 2020 Oct 05.

9/1/2020
Rambout X, Maquat LE. "The nuclear cap-binding complex as choreographer of gene transcription and pre-mRNA processing." Genes & development.. 2020 Sep 1; 34(17-18):1113-1127.

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