期刊
NUCLEIC ACIDS RESEARCH
卷 42, 期 3, 页码 1916-1929出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkt1049
关键词
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资金
- National Institutes of Health (NIH) [GM008102-3052, KO1 HL-04355-05, U54 CA96297, GM058595]
- RISE Award [2R25GM61151]
- National Center for Research Resources of the National Institute of Health [P20 RR 016174]
- National Center for Research Resources of the National Institute of Health [UPR Institutional Fund (FIPI)]
- National Center for Research Resources of the National Institute of Health [UPR Institutional Fund (PES)]
One third of inherited genetic diseases are caused by mRNAs harboring premature termination codons as a result of nonsense mutations. These aberrant mRNAs are degraded by the Nonsense-Mediated mRNA Decay (NMD) pathway. A central component of the NMD pathway is Upf1, an RNA-dependent ATPase and helicase. Upf1 is a known phosphorylated protein, but only portions of this large protein have been examined for phosphorylation sites and the functional relevance of its phosphorylation has not been elucidated in Saccharomyces cerevisiae. Using tandem mass spectrometry analyses, we report the identification of 11 putative phosphorylated sites in S. cerevisiae Upf1. Five of these phosphorylated residues are located within the ATPase and helicase domains and are conserved in higher eukaryotes, suggesting a biological significance for their phosphorylation. Indeed, functional analysis demonstrated that a small carboxy-terminal motif harboring at least three phosphorylated amino acids is important for three Upf1 functions: ATPase activity, NMD activity and the ability to promote translation termination efficiency. We provide evidence that two tyrosines within this phospho-motif (Y-738 and Y-742) act redundantly to promote ATP hydrolysis, NMD efficiency and translation termination fidelity.
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