Human PP11 (
placental protein 11) was previously described as a
serine protease specifically expressed in the syncytiotrophoblast and in numerous
tumor tissues. Several PP11-like
proteins were annotated in distantly related organisms, such as worms and mammals, suggesting their involvement in evolutionarily conserved processes. Based on sequence similarity, human PP11 was included in a
protein family whose characterized members are XendoU, a Xenopus laevis
endoribonuclease involved in
small nucleolar RNA processing, and Nsp15, an
endoribonuclease essential for coronavirus replication. Here we show that the bacterially expressed human PP11 displays
RNA binding capability and cleaves single stranded
RNA in a Mn(2+)-dependent manner at uridylates, to produce molecules with 2',3'-cyclic
phosphate ends. These features, together with structural and mutagenesis analyses, which identified the potential active site residues, reveal striking parallels to the amphibian XendoU and assign a
ribonuclease function to PP11. This newly discovered enzymatic activity places PP11-like
proteins in a completely new perspective.