Lynne E. Maquat

Lynne Elizabeth Maquat Ph.D., a member of the National Academy of Sciences, holds the J. Lowell Orbison Endowed Chair and is Professor of Biochemistry & Biophysics and of Oncology at the University of Rochester Medical Center. Professor Maquat is also Founding Director of the Center for RNA Biology and Founding Chair of Graduate Women in Science at the University of Rochester.

Lynne Elizabeth Maquat
Nationality American
Fields Biochemistry, Molecular and Cell Biology
Institutions University of Rochester
Alma mater University of Wisconsin–Madison, University of Connecticut
Known for RNA biology in human diseases

Biography

Maquat earned a B.A. degree in Biology, with a concentration in Cell Biology, from the University of Connecticut - Storrs. She was an Honors Fellow and graduated Summa cum Laude. She then obtained a Ph.D. degree in Biochemistry from the University of Wisconsin–Madison for work done with William S. Reznikoff on the E. coli lactose promoter, and did post-doctoral work at the McArdle Laboratory for Cancer Research with Jeff Ross on the human hereditary hemolytic anemias β+- and βο-thalassemias. Maquat joined the Department of Human Genetics (later changed to the Department of Cancer Genetics) at Roswell Park Cancer Institute in Buffalo, New York before moving her laboratory to the University of Rochester Medical Center.

Research

Professor Maquat is known for her mammalian-cell studies of nonsense-mediated mRNA decay (NMD), which she first reported in 1981 through studies of the anemia bo-thalassemia and from which she subsequently discovered the pioneer round of protein synthesis, the exon-junction complex (EJC), and how the EJC marks messenger (m)RNAs for a first quality-control round of protein synthesis that largely occurs as newly synthesized mRNAs leave the nucleus in which they are synthesized and enter the cytoplasm, where they have access to cytoplasmic protein-synthesis machinery. She continues to make seminal contributions on mechanisms of NMD, how NMD is utilized by cells to better adapt to changing environments, and another pathway she discovered and named Staufen-mediated mRNA decay (SMD). Her work on SMD has defined new roles for long non-coding RNAs and short interspersed elements (SINEs) in humans and rodents, unveiling the complexities of RNA interactions with other RNAs that comprise important post-transcriptional gene regulatory pathways during mammalian-cell development and differentiation.

Some seminal research accomplishments, with references, are:

  1. Discovered the human UPF2 and 3/3X nonsense-mediated mRNA decay (NMD) factors and that they constitute what the Maquat-lab had been calling the splicing-dependent “mark” and subsequently re-named (in collaboration with Melissa J. Moore) the exon-junction complex (EJC).
    • Le Hir H, Moore MJ, Maquat LE. Pre-mRNA splicing alters mRNP composition: evidence for stable association of proteins at exon-exon junctions. Genes Dev. 2000 May 1;14(9):1098-108. PubMed PMID 10809668; PubMed Central PMCID: PMC316578.
    • Le Hir H, Izaurralde E, Maquat LE, Moore MJ. The spliceosome deposits multiple proteins 20-24 nucleotides upstream of mRNA exon-exon junctions. EMBO J. 2000 Dec 15;19(24):6860-9. PubMed PMID 11118221; PubMed Central PMCID: PMC305905.
    • Serin G, Gersappe A, Black JD, Aronoff R, Maquat LE. Identification and characterization of human orthologues to Saccharomyces cerevisiae Upf2 protein and Upf3 protein (Caenorhabditis elegans SMG-4). Mol Cell Biol. 2001 Jan;21(1):209-23. PubMed PMID 11113196; PubMed Central PMCID: PMC88795.
    • Lejeune F, Ishigaki Y, Li X, Maquat LE. The exon junction complex is detected on CBP80-bound but not eIF4E-bound mRNA in mammalian cells: dynamics of mRNP remodeling. EMBO J. 2002 Jul 1;21(13):3536-45. PubMed PMID 12093754; PubMed Central PMCID: PMC126094.
  2. After showing in the 1990s that NMD in human cells targets largely newly synthesized mRNAs, discovered and characterized the pioneer translation initiation complex. This complex, which is bound at the 5’-cap by CBP80 and CBP20, supports the bulk of human-cell NMD and is a precursor to the steady-state translation initiation complex, which is bound at the cap by eIF4E and supports the bulk of cellular protein synthesis.
    • Ishigaki Y, Li X, Serin G, Maquat LE. Evidence for a pioneer round of mRNA translation: mRNAs subject to nonsense-mediated decay in mammalian cells are bound by CBP80 and CBP20. Cell. 2001 Sep 7;106(5):607-17. PubMed PMID 11551508.
    • Chiu SY, Lejeune F, Ranganathan AC, Maquat LE. The pioneer translation initiation complex is functionally distinct from but structurally overlaps with the steady-state translation initiation complex. Genes Dev. 2004 Apr 1;18(7):745-54. PubMed PMID 15059963; PubMed Central PMCID: PMC387415.
    • Lejeune F, Ranganathan AC, Maquat LE. eIF4G is required for the pioneer round of translation in mammalian cells. Nat Struct Mol Biol. 2004 Oct;11(10):992-1000. PubMed PMID 15361857.
    • Trcek T, Sato H, Singer RH, Maquat LE. Temporal and spatial characterization of nonsense-mediated mRNA decay. Genes Dev. 2013 Mar 1;27(5):541-51. PubMed PMID 23431032; PubMed Central PMCID: PMC3605467.
  3. Showed that the cap-binding protein CBP80 promotes NMD, and elucidated the mechanism by which CBP80 is replaced by eIF4E.
    • Hosoda N, Kim YK, Lejeune F, Maquat LE. CBP80 promotes interaction of Upf1 with Upf2 during nonsense-mediated mRNA decay in mammalian cells. Nat Struct Mol Biol. 2005 Oct;12(10):893-901. PubMed PMID 16186820.
    • Isken O, Kim YK, Hosoda N, Mayeur GL, Hershey JW, et al. Upf1 phosphorylation triggers translational repression during nonsense-mediated mRNA decay. Cell. 2008 Apr 18;133(2):314-27. PubMed PMID 18423202; PubMed Central PMCID: PMC4193665.
    • Sato H, Maquat LE. Remodeling of the pioneer translation initiation complex involves translation and the karyopherin importin beta. Genes Dev. 2009 Nov 1;23(21):2537-50. PubMed PMID 19884259; PubMed Central PMCID: PMC2779746.
    • Hwang J, Sato H, Tang Y, Matsuda D, Maquat LE. UPF1 association with the cap-binding protein, CBP80, promotes nonsense-mediated mRNA decay at two distinct steps. Mol Cell. 2010 Aug 13;39(3):396-409. PubMed PMID 20691628; PubMed Central PMCID: PMC2924619.
  4. Discovered Staufen-mediated mRNA decay (SMD); new roles for Staufen small interspersed elements, long non-coding RNAs and degenerate double-stranded RNA-binding domains.
    • Kim YK, Furic L, Desgroseillers L, Maquat LE. Mammalian Staufen1 recruits Upf1 to specific mRNA 3'UTRs so as to elicit mRNA decay. Cell. 2005 Jan 28;120(2):195-208. PubMed PMID 15680326.
    • Kim YK, Furic L, Parisien M, Major F, DesGroseillers L, et al. Staufen1 regulates diverse classes of mammalian transcripts. EMBO J. 2007 Jun 6;26(11):2670-81. PubMed PMID 17510634; PubMed Central PMCID: PMC1888674.
    • Gong C, Maquat LE. lncRNAs transactivate STAU1-mediated mRNA decay by duplexing with 3' UTRs via Alu elements. Nature. 2011 Feb 10;470(7333):284-8. PubMed PMID 21307942; PubMed Central PMCID: PMC3073508.
    • Gong C, Tang Y, Maquat LE. mRNA-mRNA duplexes that autoelicit Staufen1-mediated mRNA decay. Nat Struct Mol Biol. 2013 Oct;20(10):1214-20. PubMed PMID 24056942; PubMed Central PMCID: PMC3947523.
  5. Elucidated the physiological relevance of SMD and NMD and a new pathway for inverted Alu-element metabolism.
    • Gong C, Kim YK, Woeller CF, Tang Y, Maquat LE. SMD and NMD are competitive pathways that contribute to myogenesis: effects on PAX3 and myogenin mRNAs. Genes Dev. 2009 Jan 1;23(1):54-66. PubMed PMID 19095803; PubMed Central PMCID: PMC2632170.
    • Gleghorn ML, Gong C, Kielkopf CL, Maquat LE. Staufen1 dimerizes through a conserved motif and a degenerate dsRNA-binding domain to promote mRNA decay. Nat Struct Mol Biol. 2013 Apr;20(4):515-24. PubMed PMID 23524536; PubMed Central PMCID: PMC4096160.
    • Elbarbary RA, Li W, Tian B, Maquat LE. STAU1 binding 3' UTR IRAlus complements nuclear retention to protect cells from PKR-mediated translational shutdown. Genes Dev. 2013 Jul 1;27(13):1495-510. PubMed PMID 23824540; PubMed Central PMCID: PMC3713430.
    • Popp MW, Maquat LE. Attenuation of nonsense-mediated mRNA decay facilitates the response to chemotherapeutics. Nat Commun. 2015 Mar 26;6:6632. PubMed PMID 25808464; PubMed Central PMCID: PMC4375787.

Complete List of Published Work»

Honors and Awards

Professor Maquat has served on editorial boards including RNA, Mol. Cell Biol., RNA Biol., and Methods; as an elected Director, Treasurer/Secretary and President of the international RNA Society; as a member of the Public Information Committee of the American Society for Cell Biology; and as chair of U.S. National Institutes of Health study sections. She 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) and the U.S. National Academy of Sciences (2010),[1] and Batsheva de Rothschild Fellow of the Israel Academy of Sciences and Humanities (2012). Professor Maquat was awarded the William C. Rose Award from the American Society of Biochemistry and Molecular Biology (2014) and the ATHENA Award from the Rochester Business Alliance Women's Council, both for research and mentoring, in particular advocacy for women in science. In 2015 she received a Canada Gairdner International Award for uncovering the mechanism of NMD and its importance to normal and disease-associated gene expression.Among existing funding, Professor Maquat holds as Principal Investigator a National Institutes of Health Merit Award, a National Institutes of Health R01 Award, and a National Institutes of Health T32 Training Grant for graduate students, all from the National Institute of General Medical Sciences.

References

  1. ↑ Member directory

External links

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