PIR1, a novel phosphatase that exhibits high affinity to RNA ribonucleoprotein complexes

Protein tyrosine phosphatases are involved in the regulation of important cellular processes such as signal transduction, cell cycle progression, and tumor suppression. Here we report the cloning and characterization of PIR1, a novel member in the dual-specificity phosphatase subfamily of the protein tyrosine phosphatases. PIR1 also contains two stretches of arginine-rich sequences. We have shown that the recombinant PIR1 protein possessed an intrinsic phosphatase activity on phosphotyrosine-containing substrate. A unique feature of this phosphatase is that it binds directly to RNA in vitro with high affinity. In addition, we have found that PIR1 interacted with splicing factors 9G8 and SRp30C, possibly through an RNA intermediate during a yeast two-hybrid screen. PIR1 exhibited a nuclear-staining pattern that was sensitive to RNase A, but not to DNase I, suggesting that PIR1 in the cells are associated with RNA and/or ribonucleoprotein particles. Furthermore, a fraction of PIR1 showed a speckle-staining pattern that superimposed with that of the splicing factor, SC35. Taken together, our data suggest that PIR1 is a novel phosphatase that may participate in nuclear mRNA metabolism.