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.
|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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