THE RNA COMPONENT OF HUMAN TELOMERASE
THE RNA COMPONENT OF HUMAN TELOMERASE
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DOI：
10.1126/science.7544491
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发表时间：
1995-09-01
期刊：
影响因子：
56.9
通讯作者：
VILLEPONTEAU, B
中科院分区：
文献类型：
--
作者：
FENG, JL;FUNK, WD;VILLEPONTEAU, B
真核生物染色体用重复的端粒序列限制，可保护末端免受损坏和重排。端粒重复序列是由核糖酸（RNA） - 蛋白质复合物合成的。在这里，描述了人端粒酶的RNA成分的克隆，称为HTR。 HTR的模板区域包括11个核苷酸（5'-Cuaacccuaac）互补的人类端粒序列（TTAGGG）（n）。生殖线组织和肿瘤细胞系比正常的体细胞和组织表达的HTR更高，没有可检测到的端粒酶活性。在模板区域中表达HTR突变的人类细胞系产生了预测的突变端粒酶活性。 HELA细胞用反义HTR丢失的端粒DNA转染，并在双打23至26次后开始死亡。因此，人端粒酶是不朽肿瘤细胞长期增殖的关键酶。
Eukaryotic chromosomes are capped with repetitive telomere sequences that protect the ends from damage and rearrangements. Telomere repeats are synthesized by telomerase, a ribonucleic acid (RNA)-protein complex. Here, the cloning of the RNA component of human telomerase, termed hTR, is described. The template region of hTR encompasses 11 nucleotides (5'-CUAACCCUAAC) complementary to the human telomere sequence (TTAGGG)(n). Germline tissues and tumor cell lines expressed more hTR than normal somatic cells and tissues, which have no detectable telomerase activity. Human cell lines that expressed hTR mutated in the template region generated the predicted mutant telomerase activity. HeLa cells transfected with an antisense hTR lost telomeric DNA and began to die after 23 to 26 doublings. Thus, human telomerase is a critical enzyme for the long-term proliferation of immortal tumor cells.