Human cardiac troponin T: cloning and expression of new isoforms in the normal and failing heart.
Human cardiac troponin T: cloning and expression of new isoforms in the normal and failing heart.
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DOI：
10.1161/01.res.76.4.687
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发表时间：
1995-04
影响因子：
20.1
通讯作者：
L. Mesnard;D. Logeart;S. Taviaux;S. Diriong;J. Mercadier;F. Samson
中科院分区：
文献类型：
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作者：
L. Mesnard;D. Logeart;S. Taviaux;S. Diriong;J. Mercadier;F. Samson
肌钙蛋白T，像许多肌原纤维蛋白一样，作为由不同基因编码或由相同初级RNA转录物剪接产生的多种同种型存在。我们已经克隆了第一个人心肌肌钙蛋白T（cTnT）的cDNA，并显示cTnT在心肌和骨骼肌发育过程中的差异表达。在这项工作中，我们通过荧光原位杂交到1 q32定位人cTnT基因，并通过测序从人胎心cDNA文库中分离的13个cDNA，确定了三个新的异构体产生的三个可变区在人cTnT cDNA的特定组合。第一个可变区是位于cDNA的5'端的30-bp盒，其可以完全或仅从前3bp开始切除;第二个可变区是可以完全切除的密码子;第三个可变区是cDNA的3'半部分中的9-bp盒，其也可以完全或仅从前3bp切除。RNA酶保护研究证实了胎儿和成人心室中相应RNA的存在。与对照组相比，在衰竭心室中未发现胎儿亚型的蓄积。
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.