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Alternative mRNA splicing generates tissue-specific isoforms of 116-kDa polypeptide of vacuolar proton pump.

The cDNA encoding the 116-kDa polypeptide of the bovine brain vacuolar-type proton translocating ATPases has been cloned and sequenced. One of five clones differed from all others in that it contained an 18-base pair deletion within the coding region, whereas it was identical to the other clones in overlapping coding and noncoding regions, indicating that this heterogeneity arises through an alternative splicing mechanism. By conventional Northern analysis, only one 4.1-kilobase mRNA was identified in bovine brain, heart, kidney, liver, and spleen. However, a polymerase chain reaction-based analysis revealed two species of mRNA with a tissue-specific distribution. Type I, containing the 18-base pair insert, was found in brain, whereas the truncated (Type II) form was found in all tissues examined. Similar tissue distributions of rat mRNA were observed. The deletion site accounting for this variability occurs within a predicted protease sensitivity motif (PEST site), suggesting that differences in the biological half-life of the two 116-kDa isoforms may exist.