A protein tyrosine phosphatase-like protein from baculovirus has RNA 5'-triphosphatase and diphosphatase activities.
The superfamily of protein tyrosine phosphatases (PTPs) includes at least one enzyme with an RNA substrate. We recently showed that the RNA triphosphatase domain of the Caenorhabditis elegans mRNA capping enzyme is related to the PTP enzyme family by sequence similarity and mechanism. The PTP most similar in sequence to the capping enzyme triphosphatase is BVP, a dual-specificity PTP encoded by the Autographa californica nuclear polyhedrosis virus. Although BVP previously has been shown to have modest tyrosine and serine/threonine phosphatase activity, we find that it is much more potent as an RNA 5'-phosphatase. BVP sequentially removes gamma and beta phosphates from the 5' end of triphosphate-terminated RNA, leaving a 5'-monophosphate end. The activity was specific for polynucleotides; nucleotide triphosphates were not hydrolyzed. A mutant protein in which the active site cysteine was replaced with serine was inactive. Three other dual-specificity PTPs (VH1, VHR, and Cdc14) did not exhibit detectable RNA phosphatase activity. Therefore, capping enzyme and BVP are members of a distinct PTP-like subfamily that can remove phosphates from RNA.
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
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Takagi
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Taylor
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Kusakabe
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Charbonneau
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Buratowski
D017766:Acid Anhydride Hydrolases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000235:genetics; D029742:Caenorhabditis elegans Proteins; D004926:Escherichia coli / Q000235:genetics; D017924:Nucleopolyhedroviruses / Q000201:enzymology* / Q000235:genetics; D009713:Nucleotidyltransferases / Q000235:genetics / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000235:genetics / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D012313:RNA / Q000737:chemistry / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D000098556:mRNA Guanylyltransferases
D029742:Caenorhabditis elegans Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D012313:RNA; D009713:Nucleotidyltransferases; D000098556:mRNA Guanylyltransferases; C106834:CEL-1 protein, C elegans; D017027:Protein Tyrosine Phosphatases; D010727:Phosphoric Diester Hydrolases; C025672:RNA-tyrosine phosphatase; D017766:Acid Anhydride Hydrolases; C023090:RNA triphosphatase