A novel mechanism of alternative RNA splicing for the developmentally regulated generation of troponin T isoforms from a single gene.

Troponin T (TnT) is a major regulatory protein of the striated muscle that exhibits developmental and tissue-specific structural heterogeneity. The molecular basis for this heterogeneity was studied at the level of TnT structural gene organization and RNA expression. Two tissue-specific and developmentally regulated TnT mRNAs, alpha and beta, are derived from a single fast skeletal muscle TnT gene. Although otherwise structurally identical from amino acid 70 to the end of the 3' untranslated region, the alpha and beta TnT mRNAs differ by a small internal oligonucleotide coding for amino acids 229 to 242. These isoform-specific oligopeptides, both spanning the same internal portion of the TnT protein, are encoded by two distinct and adjacent miniexons in the TnT gene. Alternative and mutually exclusive splicing of these two miniexons results in the incorporation of either exon into the mature TnT mRNA and argues persuasively against a processive scanning model of RNA splice site selection.