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.