Genomic sequence and structural organization of mouse slow skeletal muscletroponin T gene

Three muscle type-specific troponin T (TnT) genes are present in vertebrate to encode a number of protein isoforms via alternative mRNA splicing. Whil e the genomic structures of cardiac and fast skeletal muscle TnT genes have been documented, this study cloned and characterized the slow skeletal mus cle TnT (sTnT) gene. Complete nucleotide sequence and genomic organization revealed that the mouse sTnT gene spans 11.1 kb and contains 14 exons, whic h is smaller and simpler than the fast skeletal muscle and cardiac TnT gene s. Potentially representing a prototype of the TnT gene family, the 5'-regi on of the sTnT gene contains fewer unsplit large exons, among which two alt ernatively spliced exons are responsible for the NH2-terminal variation of three sTnT isoforms. The sTnT gene structure shows that the alternatively s pliced central segment found in human sTnT cDNAs may be a result from splic ing using an alternative acceptor site at the intron Il-exon 12 boundary. T ogether with the well-conserved protein structure, the highly specific expr ession of sTnT in slow skeletal muscles indicates a differentiated function of this member of the TnT gene family. The determination of genomic struct ure and alternative splicing pathways of sTnT gene lays a foundation to fur ther understand the TnT structure-function evolution as well as contractile characteristics of different types of muscle fiber. (C) 1999 Elsevier Scie nce B.V. All rights reserved.