<p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p> <p>We describe the cloning, sequencing and structure of the human fast skeletal troponin T (TNNT3) gene located on chromosome 11p15.5. The single-copy gene encodes 19
exons and 18 introns. Eleven of these exons, 1–3, 9–15 and 18, are constitutively
spliced, whereas exons 4–8 are alternatively spliced. The gene contains an additional
subset of developmentally regulated and alternatively spliced exons, including a foetal
exon located between exon 8 and 9 and exon 16 or α (adult) and 17 or β (foetal and
neonatal). Exon phasing suggests that the majority of the alternatively spliced exons
located at the 5′ end of the gene may have evolved as a result of exon shuffling, because
they are of the same phase class. In contrast, the 3′ exons encoding an evolutionarily
conserved heptad repeat domain, shared by both TnT and troponin I (TnI), may be
remnants of an ancient ancestral gene. The sequence of the 5′ flanking region shows
that the putative promoter contains motifs including binding sites for MyoD, MEF-2
and several transcription factors which may play a role in transcriptional regulation
and tissue-specific expression of TnT. The coding region of TNNT3 exhibits strong
similarity to the corresponding rat sequence. However, unlike the rat TnT gene,
TNNT3 possesses two repeat regions of CCA and TC. The exclusive presence of
these repetitive elements in the human gene indicates divergence in the evolutionary
dynamics of mammalian TnT genes. Homologous muscle-specific splicing enhancer
motifs are present in the introns upstream and downstream of the foetal exon, and
may play a role in the developmental pattern of alternative splicing of the gene. The
genomic correlates of TNNT3 are relevant to our understanding of the evolution and
regulation of expression of the gene, as well as the structure and function of the protein
isoforms. The nucleotide sequence of TNNT3 has been submitted to EMBL/GenBank
under Accession No. AF026276.</p>
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Comp Funct Genomics. 2003 Dec; 4(6):609-625