Nucleolar localization of TERT is unrelated to telomerase function in human cells
Nucleolar localization of TERT is unrelated to telomerase function in human cells
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TERT 的核仁定位与人类细胞中的端粒酶功能无关
DOI：
10.1242/jcs.024091
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发表时间：
2008-07-01
影响因子：
4
通讯作者：
Huang, Jun Jian
中科院分区：
文献类型：
--
作者：
Lin, Jian;Jin, Rui;Huang, Jun Jian
端粒酶维持端粒的长度，并与人类细胞的衰老和癌变有关。这种酶是一种专门的核糖核蛋白（RNP）复合物，最低限度由两个基本组分组成：蛋白质催化亚基TERT（端粒酶逆转录酶）和整合RNA部分TR（端粒酶RNA，TERC）。已经发现TERT和TR都定位于细胞核内的核仁，从而提示核仁是人类细胞中端粒酶RNP生物合成的位点。不过，这一说法是否属实，目前还没有令人信服的论证。在这里，我们确定的人TERT多肽的残基965-981构成了一个活跃的核仁靶向信号（NTS）介导的人TERT核仁定位必不可少的。这种NTS的突变失活完全破坏了正常和恶性人类细胞中的TERT核仁易位。最有趣的是，这样的TERT突变体在BJ细胞（正常成纤维细胞）中仍然保留了激活端粒酶活性、维持端粒长度和延长细胞增殖寿命的能力，就像野生型TERT一样。因此，我们的数据表明，在人类细胞中，端粒酶的核仁定位是无关的端粒酶功能。
Telomerase maintains telomere length and has been implicated in both aging and carcinogenesis of human cells. This enzyme is a specialized ribonucleoprotein (RNP) complex, minimally consisting of two essential components: the protein catalytic subunit TERT (telomerase reverse transcriptase) and the integral RNA moiety TR (telomerase RNA, TERC). Both TERT and TR have been found to localize to nucleoli within the nucleus, leading to the suggestion of nucleoli as the site for telomerase RNP biogenesis in human cells. However, whether this statement is true or not has not yet been convincingly demonstrated. Here, we identify that residues 965-981 of the human TERT polypeptide constitute an active nucleolar-targeting signal (NTS) essential for mediating human TERT nucleolar localization. Mutational inactivation of this NTS completely disrupted TERT nucleolar translocation in both normal and malignant human cells. Most interestingly, such a TERT mutant still retained the capacity to activate telomerase activity, maintain telomere length and extend the life-span of cellular proliferation, as does wild-type TERT, in BJ cells (normal fibroblasts). Therefore, our data suggest that TERT nucleolar localization is unrelated to telomerase function in human cells.