Alternative splicing regulates the production of ARD-1 endoribonuclease and NIPP-1, an inhibitor of protein phosphatase-1, as isoforms encoded by thesame gene

ARD-I is an endoribonuclease identified initially as the product of a human cDNA that complements mutations in me, a gene that encodes Escherichia col i ribonuclease E. NIPP-1 was identified in bovine nuclear extracts as an in hibitor of protein phosphatase-l. Earlier work has shown that the protein-c oding sequence of ARD-I is identical to the carboxy-terminal third of NIPP- 1. However, whether ARD-1 is present in eukaryotes as a distinct entity has been unclear, as neither ARD-l-specific transcripts nor ARD-I protein were detected in mammalian cells in earlier studies. Here we show that ARD-1 ex ists in human cells as a discrete protein, and that the ARD-1 and NIPP-1 pe ptides are isoforms encoded by a single gene and the same alternatively spl iced precursor RNA. A retained intron containing multiple translation stop codons that are configured to terminate translation and initiate nonsense-m ediated decay, limits the production of cellular ARD-1 protein. Our results establish the process by which functionally disparate ARD-I and NIPP-1 pep tides are generated from the protein-coding sequence of the same gene in hu man cells. (C) 1999 Elsevier Science B.V. AU rights reserved.