Physiologically regulated alternative splicing patterns of fast troponin T RNA are conserved in mammals

Abstract

NH2-terminal isoforms of fast troponin T (TnT) are generated by alternative splicing of fast TnT RNA transcripts. Significantly different estimates for the number of isoforms have been obtained by nucleic acid and protein chemical studies. To resolve this controversy and to determine whether specific 5'-splicing patterns correlate with fiber phenotype, we generated representative populations of 5'-TnT cDNAs from the TnT mRNAs expressed in a set of physiologically and anatomically diverse skeletal muscles. Sequencing and restriction enzyme analyses revealed a total of nine cDNAs that encode the six adult and three perinatal NH2-terminal TnT variants previously identified. Three major 5'-splicing pathways (the TnT1f, TnT2f, and TnT3f patterns) account for more than 90% of the TnT mRNAs and proteins in adult rabbit skeletal muscle. Comparative studies in rats, mice, and humans show that these splicing patterns are conserved and that fast-twitch fibers that are primarily glycolytic utilize the TnT1f and TnT2f patterns preferentially, whereas fast-twitch fibers that are primarily oxidative use the TnT1f and TnT3f patterns preferentially.