Organization and alternate splice products of the gene encoding nuclear inhibitor of protein phosphatase-1 (NIPP-1)

Nuclear inhibitor of protein phosphatase-1 (NIPP-1) is one of two major reg ulatory subunits of protein phosphatase-1 in mammalian nuclei. We report he re the cloning and structural characterization of the human NIPP-1 genes, d esignated PPP1R8P and PPP1R8 in human gene nomenclature. PPP1R8P (1.2 kb) i s a processed pseudogene and was localized by in situ hybridization to chro mosome 1p33-32, PPP1R8 is an authentic NIPP-1 gene and was localized to chr omosome 1p35. PPP1R8 (25.2 kb) is composed of seven exons and encodes four different transcripts, as determined from cDNA library screening, reverse t ranscriptase-PCR (RT-PCR) and/or EST (expressed sequence tag) database sear ch analysis. NIPP-1 alpha mRNA represents the major transcript in human tis sues and various cell lines, and encodes a polypeptide of 351 residues that only differs from the previously cloned calf thymus NIPP-1 by a single res idue. The other transcripts, termed NIPP-1 beta, gamma and delta, are gener ated by alternative 5'-splice site usage, by exon skipping and/or by altern ative polyadenylation. The NIPP-1 beta/delta and NIPP-1 gamma mRNAs are exp ected to encode fragments of NIPP-1 alpha that differ from the latter by th e absence of the first 142 and 224 residues, respectively. NIPP-1 gamma, co rresponds to 'activator of RNA decay-1' (Ard-1) which, unlike NIPP-1 alpha, displays in vitro and endoribonuclease activity and lacks an RVXF consensu s motif for interaction with protein phosphatase-1. While the NIPP-1 alpha/ beta/delta-transcripts were found to be present in various human tissues, t he NIPP-1 gamma transcript could only be detected in human transformed B-ly mphocytes.