Human PIR1 of the protein-tyrosine phosphatase superfamily has RNA 5'-triphosphatase and diphosphatase activities.
A human cDNA was isolated encoding a protein with significant sequence similarity (41% identity) to the BVP RNA 5'-phosphatase from the Autographa californica nuclear polyhedrosis virus. This protein is a member of the protein-tyrosine phosphatase (PTP) superfamily and is identical to PIR1, shown by Yuan et al. (Yuan, Y., Da-Ming, L., and Sun, H. (1998) J. Biol. Chem. 272, 20347-20353) to be a nuclear protein that can associate with RNA or ribonucleoprotein complexes. We demonstrate that PIR1 removes two phosphates from the 5'-triphosphate end of RNA, but not from mononucleotide triphosphates. The specific activity of PIR1 with RNA is several orders of magnitude greater than that with the best protein substrates examined, suggesting that RNA is its physiological substrate. A 120-amino acid segment C-terminal to the PTP domain is not required for RNA phosphatase activity. We propose that PIR1 and its closest homologs, which include the metazoan mRNA capping enzymes, constitute a subgroup of the PTP family that use RNA as a substrate.
Deshpande
T
T
Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907, USA.
Takagi
T
T
Hao
L
L
Buratowski
S
S
Charbonneau
H
H
D017766:Acid Anhydride Hydrolases / Q000378:metabolism*; D000595:Amino Acid Sequence; D020134:Catalytic Domain; D002460:Cell Line; D054637:Dual-Specificity Phosphatases; D004926:Escherichia coli; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment
D005982:Glutathione Transferase; C114064:DUSP11 protein, human; D054637:Dual-Specificity Phosphatases; D017027:Protein Tyrosine Phosphatases; D017766:Acid Anhydride Hydrolases; C023090:RNA triphosphatase