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Lynne Elizabeth Maquat, Ph.D.

Contact Information

Phone Numbers

Office: (585) 273-5640

Fax: (585) 271-2683

Biography

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 By the time CBP80 and CBP20 have been replaced by eIF4E, the Upf mark has been removed so that mRNA is largely immune to NMD.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

Faculty Appointments

  • Professor - Department of Biochemistry and Biophysics (SMD) - Primary
  • Professor - Cancer Center
  • J. Lowell Orbison Distinguished Service Alumni Professorship- Department of Dean's Office, SMD (SMD)
  • Director, Center for RNA Biology- Department of Office of VP for Health Sciences (URMC)

Education

1979
PhD | Univ Wisconsin-Madison
Biochemistry

1974
BA | University of Connecticut
Biology

Awards

2017
2017 International RNA Society Lifetime Achievement in Science Award
Sponsor: RNA Society
Location: Prague, Czech Republic

2015
Canada Gairdner International Award
Sponsor: The Gairdner Foundation

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

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

2013 - Present
MERIT Award from the NIH GM

2013
Presidential Diversity Award
Sponsor: University of Rochester

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

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 Association for the Advancement of Science
Sponsor: American Association for the Advancement of Science

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

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

Title: Compositions and Methods for Treating Cancer
U.S. Serial #: 15/082,750
Filed: Mar 28, 2016
Invented By: LynneMaquat, MaximilianPopp

Title: Methods and Compositions Related to Staufen 1 Binding Sites Formed By Duplexing ALU Elements
U.S. Serial #: 13/984,709
Filed: Feb 09, 2012
Invented By: ChenguangGong, LynneMaquat

Publications

Journal Articles

9/30/2016
Gleghorn ML, Zhao J, Turner DH, Maquat LE. "Crystal structure of a poly(rA) staggered zipper at acidic pH: evidence that adenine N1 protonation mediates parallel double helix formation." Nucleic acids research.. 2016 Sep 30; 44(17):8417-24. Epub 2016 Jun 10.

6/2/2016
Popp MW, Maquat LE. "Leveraging Rules of Nonsense-Mediated mRNA Decay for Genome Engineering and Personalized Medicine." Cell.. 2016 Jun 2; 165(6):1319-22.

4/2016
Maquat LE. "Eukaryotic antisense ahead of its time." Nature reviews. Molecular cell biology.. 2016 Apr; 17(4):204. Epub 2016 Feb 24.

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