Lynne Elizabeth Maquat, Ph.D.

Lynne Elizabeth Maquat, Ph.D.

Contact Information

University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 712
Rochester, NY 14642

Office: (585) 273-5640
Fax: (585) 271-2683

Lab Information

Maquat Lab

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Research Bio

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 By the time CBP80 and CBP20 have been replaced by eIF4E, the Upf mark has been removed so that mRNA is immune to NMD.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

We have also uncovered a new mRNA decay pathway that we call Staufen (Stau)1-mediated mRNA decay (SMD). This pathway provides cells with a previously unappreciated means to regulate gene expression posttranscriptionally. We have found that the double-stranded RNA binding protein Stau1 recruits the NMD factor Upf1 to mRNAs, a number of which have been identified using microarray analysis in collaboration with Luc DesGroseillers (Université de Montréal). For those mRNAs that we have studied in detail, Stau1 recruits Upf1 to the 3' UTR and elicits mRNA decay in way that depends on translation termination at the normal (i.e., upstream) termination codon. By so doing, Stau1 bypasses the need for the Upf3 or Upf3X and Upf2 NMD factors, which serve to recruit Upf1 during NMD. More recent microarray and other types of analyses of mRNAs that are upregulated when Stau1 is downregulated indicate that SMD is widely used by cells as a means of posttranscriptional control.

Please visit our lab website for more information.

Patents

Using and/or Targeting Long Non-Coding RNAs to Regulate Gene Expression

United States Serial NO.: 13/984,709
Filed Date: February 9, 2012
Title: Methods and Compositions Related to Staufen 1 Binding Sites Formed By Duplexing ALU Elements
Invented by: Lynne Maquat, Chenguang Gong

Awards & Honors (National)

William C. Rose Award | American Society of Biochemistry and Molecular Biology 2014
Batsheva de Rothschild Fellow of the Israel Academy of Sciences and Humanities 2012 - Present
Elected to the National Academy of Sciences | National Academy of Sciences 2011
RNA Society Lifetime Achievement Award in Service | RNA Society 2010
Elected to the American Association for the Advancement of Science 2006
Elected to the American Academy of Arts and Sciences | American Academy of Arts and Sciences 2006
RPI/RNA Award for most significant paper co-authored by a junior scientist published in RNA | RNA Jornal 1998
Exemplary "Woman in Government" | New York State Commissioner of Health 1990
American Heart Association Established Investigatorship | American Heart Association 1985 - 1989

Awards & Honors (Local)

Presidential Diversity Award | University of Rochester 2013
Davey Memorial Award for Outstanding Cancer Research | Wilmot Cancer Center, URMC 2002

Recent Journal Articles

Showing the 5 most recent journal articles. 111 available »

2014 Jan 30
Popp MW, Maquat LE. "The dharma of nonsense-mediated mRNA decay in Mammalian cells." Molecules and cells.. 2014 Jan 30; 37(1):1-8. Epub 2014 Jan 27.
2013 Oct
Gong C, Tang Y, Maquat LE. "mRNA-mRNA duplexes that autoelicit Staufen1-mediated mRNA decay." Nature structural & molecular biology. 2013 Oct; 20(10):1214-20. Epub 2013 Sep 22.
2013 May 24
Wang J, Lucas BA, Maquat LE. "New gene expression pipelines gush lncRNAs." Genome biology. 2013 May 24; 14(5):117. Epub 2013 May 24.
2013 Apr 1
Wang J, Gong C, Maquat LE. "Control of myogenesis by rodent SINE-containing lncRNAs." Genes & development. 2013 Apr 1; 27(7):793-804. Epub 2013 Apr 04.
2013 Apr
Gleghorn ML, Gong C, Kielkopf CL, Maquat LE. "Staufen1 dimerizes through a conserved motif and a degenerate dsRNA-binding domain to promote mRNA decay." Nature structural & molecular biology. 2013 Apr; 20(4):515-24. Epub 2013 Mar 24.

Current Appointments

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

Education

PhD | Biochemistry | Univ Wisconsin-Madison1979
BA | Biology | University of Connecticut1974