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Lynne Elizabeth Maquat, Ph.D.
Lynne Elizabeth Maquat, Ph.D.

Lynne Elizabeth Maquat, Ph.D.

Lynne Elizabeth Maquat, Ph.D.


Locations

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

(585) 273-5640

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Fax

(585) 271-2683

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 By the time CBP80 and CBP20 have been replaced by eIF4E, the Upf mark has been removed so that mRNA is largely immune to NMD.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

Publications:

Elbarbary RA, Miyoshi K, Myers JR, Du P, Ashton JM, Tian B, Maquat LE. "Tudor-SN-mediated endonucleolytic decay of human cell microRNAs promotes G1/S phase transition." Science.. 2017 May 26; 356(6340):859-862.

Elbarbary RA, Maquat LE. "Distinct mechanisms obviate the potentially toxic effects of inverted-repeat Alu elements on cellular RNA metabolism." Nature structural & molecular biology.. 2017 24(6):496-498.

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.

View All Publications

Links:

Lab Website

Center for RNA Biology