Identification and functional analysis of novel phosphorylation sites in the RNA surveillance protein Upf1
| Autor: | Andrea V. Rivera, Carlos I. González, Dina Paola Bracho, Alfredo Leon, Maria E. Correa, José A. González-Feliciano, Miles F. Wilkinson, Luis A. Estrella, Iván J. Cajigas, Irving E. Vega, Eva N. Rodríguez-Cruz, Clarivel Lasalde |
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| Rok vydání: | 2014 |
| Předmět: |
Saccharomyces cerevisiae Proteins
Peptide Chain Termination ATPase Nonsense-mediated decay Saccharomyces cerevisiae Amino Acid Motifs Molecular Sequence Data Sequence alignment 03 medical and health sciences Mice 0302 clinical medicine Information and Computing Sciences Genetics Animals Humans Amino Acid Sequence Phosphorylation Peptide sequence 030304 developmental biology Adenosine Triphosphatases 0303 health sciences biology Translational Helicase RNA Peptide Chain Termination Translational Biological Sciences biology.organism_classification Nonsense Mediated mRNA Decay Biochemistry biology.protein Tyrosine Sequence Alignment 030217 neurology & neurosurgery RNA Helicases Environmental Sciences Developmental Biology |
| Zdroj: | Nucleic acids research, vol 42, iss 3 Nucleic Acids Research |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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