MULTIPLE TRANSCRIPTS FOR RAT NUCLEOSIDE DIPHOSPHATE KINASE ALPHA-ISOFORM ARE STRUCTURALLY CATEGORIZED INTO 2 GROUPS THAT EXHIBIT CELL-SPECIFIC EXPRESSION AND DISTINCT TRANSLATION POTENTIAL

Rat nucleoside diphosphate (NDP) kinase is composed of two isoforms (a lpha and beta) encoded by independent genes. The mRNAs are expressed u biquitously; however, the level of expression is tissue-dependent and is also up- or down-regulated under certain conditions, including grow th stimulation, differentiation, and tumor metastasis. To address the regulatory mechanisms of gene expression for the rat NDP kinase major isoform alpha (an nm23-H2/PuF homologue), we identified the transcript ion initiation sites in detail by RNase protection and 5'-rapid amplif ication of DNA ends and located the core promoter region by chloramphe nicol acetyltransferase assay. The transcripts, initiated from an extr aordinarily wide range of sites, were categorized into two groups; one transcribed from an upstream region was spliced in the untranslated r egion (group 1), whereas the other initiated in the downstream region was not (group 2). RNase protection demonstrated that the group 1 mRNA was the dominant form present in all tissues except heart and skeleta l muscle. In situ hybridization revealed cell specific expression of t hese mRNA species, Furthermore, they differed in the translational eff iciency (the group 2 alpha > beta > the group 1 alpha). These findings suggest that the regulation of the NDP kinase expression at both tran scriptional and posttranscriptional steps could be fundamentally gover ned by the selection of transcription initiation sites.