Feng J, Funk W D, Wang S S, Weinrich S L, Avilion A A, Chiu C P, Adams R R, Chang E, Allsopp R C, Yu J
Geron Corporation, Menlo Park, CA 94025, USA.
Science. 1995 Sep 1;269(5228):1236-41. doi: 10.1126/science.7544491.
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.
真核生物染色体的末端带有重复的端粒序列，这些序列可保护染色体末端免受损伤和重排。端粒重复序列由端粒酶合成，端粒酶是一种核糖核酸（RNA）-蛋白质复合物。本文描述了人类端粒酶RNA组分（称为hTR）的克隆。hTR的模板区域包含11个与人类端粒序列（TTAGGG）n互补的核苷酸（5'-CUAACCCUAAC）。生殖系组织和肿瘤细胞系表达的hTR比正常体细胞和组织更多，而正常体细胞和组织没有可检测到的端粒酶活性。在模板区域发生突变的表达hTR的人类细胞系产生了预测的突变端粒酶活性。用反义hTR转染的HeLa细胞在23至26次倍增后失去端粒DNA并开始死亡。因此，人类端粒酶是永生化肿瘤细胞长期增殖的关键酶。
