The specific goal of the proposed research is to expand the understanding of selenoprotein RNA metabolism in mammalian cells. However, the investigator's findings will likely apply to other nonsense-containing transcripts and lend important insight into the cis-acting sequences and trans-acting factors either promote or inhibit nonsense-mediated mRNA decay (NMD).
The specific aims are to: 1. Achieve insight into the mechanism by which the premature termination of GPx1 mRNA translation at the position of the Sec codon mediates cytoplamic mRNA decay. 2. Determine why premature termination of PHGPx mRNA translation at the position of the Sec codon fails to mediate a significant reduction in PHGPx mRNA abundance.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
7R01GM059614-02
Application #
6181505
Study Section
Molecular Biology Study Section (MBY)
Program Officer
Rhoades, Marcus M
Project Start
1999-08-01
Project End
2003-07-31
Budget Start
2000-08-01
Budget End
2001-07-31
Support Year
2
Fiscal Year
2000
Total Cost
$275,358
Indirect Cost
Name
University of Rochester
Department
Biochemistry
Type
Schools of Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
Walter, Nils G; Maquat, Lynne E (2018) Introduction-RNA: From Single Molecules to Medicine. Chem Rev 118:4117-4119
Popp, Maximilian W; Maquat, Lynne E (2018) Nonsense-mediated mRNA Decay and Cancer. Curr Opin Genet Dev 48:44-50
Kurosaki, Tatsuaki; Maquat, Lynne E (2018) Molecular autopsy provides evidence for widespread ribosome-phased mRNA fragmentation. Nat Struct Mol Biol 25:299-301
Cho, Hana; Rambout, Xavier; Gleghorn, Michael L et al. (2018) Transcriptional coactivator PGC-1? contains a novel CBP80-binding motif that orchestrates efficient target gene expression. Genes Dev 32:555-567
Kurosaki, Tatsuaki; Hoque, Mainul; Maquat, Lynne E (2018) Identifying Cellular Nonsense-Mediated mRNA Decay (NMD) Targets: Immunoprecipitation of Phosphorylated UPF1 Followed by RNA Sequencing (p-UPF1 RIP-Seq). Methods Mol Biol 1720:175-186
Popp, Maximilian W; Maquat, Lynne E (2016) Leveraging Rules of Nonsense-Mediated mRNA Decay for Genome Engineering and Personalized Medicine. Cell 165:1319-1322
Elbarbary, Reyad A; Maquat, Lynne E (2016) Coupling pre-mRNA splicing and 3' end formation to mRNA export: alternative ways to punch the nuclear export clock. Genes Dev 30:487-8
Kurosaki, Tatsuaki; Maquat, Lynne E (2016) Nonsense-mediated mRNA decay in humans at a glance. J Cell Sci 129:461-7
Maquat, Lynne E (2016) Eukaryotic antisense ahead of its time. Nat Rev Mol Cell Biol 17:204
Popp, Maximilian W; Maquat, Lynne E (2015) Attenuation of nonsense-mediated mRNA decay facilitates the response to chemotherapeutics. Nat Commun 6:6632

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