Caveolin-1 isoforms are encoded by distinct mRNAs - Identification of mouse caveolin-1 mRNA variants caused by alternative transcription initiation and splicing

By searching the EST database with the known cDNA sequence encoding alpha-c aveolin-1 (full-length: FL), we found a variant having a hitherto unknown s equence in place of the first exon (5'-end variant: 5'V), The expression le vel of 5'V mRNA was equivalent to that of FL mRNA, The entire sequences of FL and 5'V mRNA were determined by 3'- and 5'-RACE analysis; their sizes we re 2484 bp and 2533 bp, respectively, and the sequences were identical exce pt for the region of the first exon, By Northern blotting, FL and 5'V mRNAs showed the same tissue distribution, and were intensely expressed in the l ung, heart, and skeletal muscle. Analyzing the protein production from thes e mRNAs using green fluorescent protein as a tag, we found FL mRNA to produ ce the alpha-isoform predominantly, but to form little beta-isoform, The pr oduction of the beta-isoform from 5'V mRNA was also demonstrated. By sequen ce analysis of the first intron of the caveolin-1 gene, a TATA box was foun d at 28 bp upstream of the transcription initiation site for 5'V mRNA. This is the first demonstration of caveolin-1 mRNA variants generated by altern ative transcription initiation, and it indicates that the two isoforms of c aveolin-1 are produced from two distinct mRNAs. (C) 2000 Federation of Euro pean Biochemical Societies.