© 1995 American Heart Association, Inc.
Articles |
Human Cardiac Troponin T: Cloning and Expression of New Isoforms in the Normal and Failing Heart
From the Laboratoire de Cardiologie Moléculaire et Cellulaire (L.M., D.L., J.J.M., F.S.), Université de Paris XI, CNRS URA 1159, Hôpital Marie Lannelongue, Le Plessis Robinson, France, and the Centre de Recherches de Biochimie Macromoléculaire (S.T., S.D.), CNRS UPR 9008, Montpellier, France.
Correspondence to Dr J.J. Mercadier, CNRS URA 1159, Hôpital Marie Lannelongue, 133 Avenue de la Résistance, 92350 Le Plessis Robinson, France.
Abstract Troponin T, like many myofibrillar proteins, exists as multiple isoforms encoded by distinct genes or generated by splicing of the same primary RNA transcript. We have previously cloned the first human cardiac troponin T (cTnT) cDNA and showed the differential expression of cTnT in cardiac and skeletal muscle during ontogenic development. In this work we located the human cTnT gene by means of fluorescent in situ hybridization to 1q32 and, by sequencing thirteen cDNAs isolated from a human fetal heart cDNA library, identified three new isoforms resulting from specific combinations of three variable regions in human cTnT cDNA. The first variable region is a 30-bp box located at the 5' end of the cDNA, which can be excised either totally or only from the first 3 bp onwards; the second is a codon which can be completely excised; and the third is a 9-bp box in the 3' half of the cDNA, which can also be excised either totally or only from the first 3 bp. The existence of the corresponding RNAs in fetal and adult ventricles was confirmed by RNase protection studies. No accumulation of the fetal isoforms was found in failing ventricles compared with controls.
Key Words: troponin T • human heart • alternative splicing
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