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Regulation of the Nonsense‐Mediated mRNA Decay Pathway in Saccharomyces cerevisiae
Author(s) -
RodríguezCruz Evan Nilda,
Cádiz Brenda,
León Alfredo,
González Carlos Iván
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a654-b
Subject(s) - phosphorylation , nonsense mediated decay , saccharomyces cerevisiae , biology , dephosphorylation , kinase , yeast , microbiology and biotechnology , gene , messenger rna , nonsense , genetics , phosphatase , rna , rna splicing
Nonsense‐mediated mRNA decay (NMD) is a RNA surveillance pathway which degrades mRNAs harboring premature termination codons (PTCs). Two conserved polypeptides essential for NMD, Upf1 and Upf2, are phosphorylated in higher eukaryotes. The phosphorylation and dephosphorylation of at least Upf1 appear to be crucial for NMD. We have recently shown that Upf1 and Upf2p are also phosphoproteins in yeast. Moreover, our studies suggest that phosphorylation of yeast Upf2p is required for NMD activity. Potential phosphorylation sites have been identified and sequence alignment of the yeast Upf1p with human and Drosophila Upf1p shows conservation in these sites. The phosphorylation of Upf1 in C. elegans is mediated by SMG‐1, a phosphatidylinositol 3‐kinase (PI3‐K) related protein kinase. The TOR1 and TOR2 genes were identified as potential candidates for the yeast orthologue of SMG‐1. To test the possible role of TOR1 or TOR2 in NMD, we monitored the decay rates of several wild type and nonsense‐containing mRNAs in tor1 − and tor2 − strains. These studies suggest that the role of Tor1p in mRNA turnover is transcript‐specific and includes both, PTC‐containing transcripts and wild‐type mRNAs. Ongoing experiments focus on the phosphorylation status of Upf1p and Upf2p in tor1 − cells. Our results indicate that phosphorylation of Upf1p and Upf2p is a conserved event in eukaryotes. These studies should provide more insights into the regulation of the NMD pathway by phosphorylation of its components. E.N.R. is supported by a graduate fellowship from PR‐AABRE (NIH Grant Number P20 RR‐016470) .