A single cardiac troponin T gene generates embryonic and adult isoforms via developmentally regulated alternate splicing

Abstract

A single cardiac troponin T gene generates two mRNA products by developmentally regulated alternate splicing. Nucleotide sequence of the entire 18 exon gene and both representative cDNAs demonstrate that the two mRNAs differ by the presence or absence of a single internal coding exon. Both mRNA products appear to be generated from a single primary transcript; however, one mRNA splice product predominates in early embryonic cardiac muscle while the other vastly predominates in adult cardiac muscle. The corresponding embryonic and adult cardiac troponin T proteins differ by the inclusion or exclusion, respectively, of an internal, highly acidic 10 amino acids near the amino terminus. Unusual features of the variable peptide region and its restriction to embryonic stages suggest that it might play a specialized role during sarcomere assembly in embryonic striated muscle. In addition to developmental regulation of RNA processing, the cardiac troponin T gene also demonstrates complex tissue-specific expression. We have previously shown that this single cardiac troponin gene is regulated according to two different and tissue-specific regulatory programs. Here we demonstrate that a single promoter is utilized for both expression patterns. The cardiac troponin T gene also has several interesting structural features including a pseudoexon and an exon only six nucleotides in length. The size of this exon establishes a new lower limit for the number of nucleotides that can be recognized as an exonic sequence.