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Professor of Biochemistry and Biophysics
Chair, University of Rochester Graduate Women in Science
Director, University of Rochester Center for RNA Biology: From Genome to Medicine
Ph.D. University of Wisconsin - Madison

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 By the time CBP80 and CBP20 have been replaced by eIF4E, the Upf mark has been removed so that mRNA is immune to NMD.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

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Recent Publications

Woeller CF, Gaspari M, Isken O, Maquat LE (2008) NMD resulting from encephalomyocarditis virus IRES-directed translation initiation seems to be restricted to CBP80/20-bound mRNA. EMBO Rep, 9:446-51

Saltzman AL, Kim YK, Pan Q, Fagnani MM, Maquat LE, Blencowe BJ (2008) Regulation of multiple core spliceosomal proteins by alternative splicing-coupled nonsense-mediated mRNA decay. Mol Cell Biol, 28:4320-30

Sato H, Hosoda N, Maquat LE (2008) Efficiency of the pioneer round of translation affects the cellular site of nonsense-mediated mRNA decay. Mol Cell, 29:255-62

Isken O, Maquat LE (2008) The multiple lives of NMD factors: balancing roles in gene and genome regulation. Nat Rev Genet,

Isken O, Kim YK, Hosoda N, Mayeur GL, Hershey JW, Maquat LE (2008) Upf1 phosphorylation triggers translational repression during nonsense-mediated mRNA decay. Cell, 133:314-27

Matsuda D, Hosoda N, Ki Kim Y, Maquat LE (2007) Failsafe nonsense-mediated mRNA decay does not detectably target eIF4E-bound mRNA. Nat Struct Mol Biol,

Kim YK, Furic L, Parisien M, Major F, Desgroseillers L, Maquat LE (2007) Staufen1 regulates diverse classes of mammalian transcripts. Embo J, 26:2670-81

Isken O, Maquat LE (2007) Quality control of eukaryotic mRNA: safeguarding cells from abnormal mRNA function. Genes Dev, 21:1833-56

Kuzmiak HA, Maquat LE (2006) Applying nonsense-mediated mRNA decay research to the clinic: progress and challenges. Trends Mol Med, 12:306-16

Pan Q, Saltzman AL, Kim YK, Misquitta C, Shai O, Maquat LE, Frey BJ, Blencowe BJ (2006) Quantitative microarray profiling provides evidence against widespread coupling of alternative splicing with nonsense-mediated mRNA decay to control gene expression. Genes Dev, 20:153-8

Hosoda N, Lejeune F, Maquat LE (2006) Evidence that poly(A) binding protein C1 binds nuclear pre-mRNA poly(A) tails. Mol Cell Biol, 26:3085-97

Kim YK, Maquat LE (2006) Staufen1-mediated mRNA decay: A Upf1-dependent pathway. Nonsense-mediated mRNA decay . In: Nonsense-Mediated mRNA Decay, ed Lynne E. Maquat, Landes Bioscience, Austin, TX, pp 229-236

Maquat LE (2006) Nonsense-mediated mRNA decay in mammalian cells: A history. Nonsense-mediated mRNA decay. In: Nonsense-Mediated mRNA Decay, ed. Lynne E. Maquat, Landes Bioscience, Georgetown,TX,, pp 43-69

Hosoda N, Kim YK, Lejeune F, Maquat LE (2005) CBP80 promotes interaction of Upf1 with Upf2 during nonsense-mediated mRNA decay in mammalian cells. Nat Struct Mol Biol, 12:893-901

Maquat LE (2005) Nonsense-mediated mRNA decay in mammals. J Cell Sci, 118:1773-6

Gao Q, Das B, Sherman F, Maquat LE (2005) Cap-binding protein 1-mediated and eukaryotic translation initiation factor 4E-mediated pioneer rounds of translation in yeast. Proc Natl Acad Sci U S A, 102:4258-63

Lejeune F, Maquat LE (2005) Mechanistic links between nonsense-mediated mRNA decay and pre-mRNA splicing in mammalian cells. Curr Opin Cell Biol, 17:309-15

Kim YK, Furic L, Desgroseillers L, Maquat LE (2005) Mammalian Staufen1 recruits Upf1 to specific mRNA 3'UTRs so as to elicit mRNA decay. Cell, 120:195-208

Lejeune F, Maquat LE (2005) RNA Processing and Human Disorders. In: Encyclopedia of the Life Sciences, ed. D. Cooper, Nature Publishing Group, London, and John Wiley & Sons, Ltd. www.els.net , (doi: 10.1038/npg.els.0005495)

Lejeune F, Ranganathan AC, Maquat LE (2004) eIF4G is required for the pioneer round of translation in mammalian cells. Nat Struct Mol Biol, 11:992-1000

Valencia-Sanchez MA, Maquat LE (2004) An enemy within: fly reconnaissance deploys an endonuclease to destroy nonsense-containing mRNA. Trends Cell Biol, 14:594-597

Brumbaugh KM, Otterness DM, Geisen C, Oliveira V, Brognard J, Li X, Lejeune F, Tibbetts RS, Maquat LE, Abraham RT (2004) The mRNA Surveillance Protein hSMG-1 Functions in Genotoxic Stress Response Pathways in Mammalian Cells. Mol Cell, 14:585-98

Maquat LE (2004) Nonsense-mediated mRNA decay: splicing, translation and mRNP dynamics. Nat Rev Mol Cell Biol, 5:89-99

Chiu SY, Lejeune F, Ranganathan AC, Maquat LE (2004) The pioneer translation initiation complex is functionally distinct from but structurally overlaps with the steady-state translation initiation complex. Genes Dev, 18:745-54

Maquat LE (2004) Nonsense-Mediated mRNA decay: A comparative analysis of different species. Current Genomics, 5:175-190

Lejeune F, Maquat LE (2004) Immunopurification and analysis of protein and RNA components of mRNP in mammalian cells. Methods Mol Biol, 257:115-24

Lejeune F, Li X, Maquat LE (2003) Nonsense-mediated mRNA decay in mammalian cells involves decapping, deadenylating, and exonucleolytic activities. Mol Cell, 12:675-87

Arraiano CM, Maquat LE (2003) Post-transcriptional control of gene expression: effectors of mRNA decay. Mol Microbiol, 49:267-76

Chiu SY, Serin G, Ohara O, Maquat LE (2003) Characterization of human Smg5/7a: a protein with similarities to Caenorhabditis elegans SMG5 and SMG7 that functions in the dephosphorylation of Upf1. RNA, 9:77-87

Maquat LE (2003) Nonsense-mediated mRNA decay in mammalian cells: From pre-mRNA processing to mRNA translation and degradation. Translation Mechanisms, eds Jacques Lapointe and Lea Brakier-Gingras, Landes Bioscience, Austin, TX, 213-222

Stevens A, Wang Y, Bremer K, Zhang J, Hoepfner R, Antoniou M, Schoenberg DR, Maquat LE (2002) Beta -Globin mRNA decay in erythroid cells: UG site-preferred endonucleolytic cleavage that is augmented by a premature termination codon. Proc Natl Acad Sci U S A, 99:12741-6

Maquat LE (2002) Molecular biology. Skiing toward nonstop mRNA decay. Science, 295:2221-2

Maquat LE (2002) Nonsense-mediated mRNA decay. Curr Biol, 12:R196-7

Maquat LE (2002) NASty effects on fibrillin pre-mRNA splicing: another case of ESE does it, but proposals for translation-dependent splice site choice live on. Genes Dev, 16:1743-53

Lejeune F, Ishigaki Y, Li X, Maquat LE (2002) The exon junction complex is detected on CBP80-bound but not eIF4E-bound mRNA in mammalian cells: dynamics of mRNP remodeling. Embo J, 21:3536-45

Maquat LE (2002) RNA-protein interactions: insight into gene function. Methods, 26:93-4

Sun X, Maquat LE (2002) Nonsense-mediated decay: assaying for effects on selenoprotein mRNAs. Methods Enzymol, 347:49-57

Maquat LE, Serin G (2002) Nonsense-mediated mRNA decay: Insights into mechanism from the cellular abundance of human Upf1, Upf2, Upf3 and Upf3X proteins. In Cold Spring Harbor Symposia on Quantitative Biology. The Ribosome, 66:313-320

Sun X, Maquat LE (2002) Nonsense-Mediated Decay: Assaying for Effects on Selenoprotein mRNAs. In Methods in Enzymology. Protein Sensors of Reactive Oxygen Species: Selenoproteins, Thioredoxin, Thiol Enzymes, and Proteins, eds. H. Sies, L. Packer, Academic Press, 347:49-57

Graduate students in my laboratory work toward a Ph.D. degree in the following program[s]:

Ph.D. in Biochemistry
Ph.D. in Biophysics

Ph.D. candidates in my laboratory may also be affiliated with these programs:

Contact Information

E-Mail: Lynne_Maquat@urmc.rochester.edu

Lynne E. Maquat Ph.D.
Department of Biochemistry and Biophysics
University of Rochester School of Medicine and Dentistry
601 Elmwood Ave, Box 712
Rochester, New York 14642

Office: Medical Center 3-8507C
Telephone: (585) 273-5640; Fax: (585) 271-2683