Constitutive and regulated expression of telomerase reverse transcriptase (hTERT) in human lymphocytes
Constitutive and regulated expression of telomerase reverse transcriptase (hTERT) in human lymphocytes
复制标题
DOI：
10.1073/pnas.96.9.5147
复制
发表时间：
1999-04-27
影响因子：
11.1
通讯作者：
Weng, NP
中科院分区：
文献类型：
--
作者：
Liu, KB;Schoonmaker, MM;Weng, NP
人端粒酶由端粒酶RNA模板（hTER）和端粒酶逆转录酶（hTERT）两种基本成分组成，其功能是合成端粒重复序列，从而保护染色体的完整性和延长细胞的复制寿命。端粒酶活性选择性地在生殖细胞和恶性肿瘤细胞中表达，而在大多数正常人体细胞中不表达。作为一个显著的例外，端粒酶在人类淋巴细胞的发育、分化和活化过程中表达。最近的研究表明，端粒酶的调节是由hTERT而不是hTER的转录决定的。端粒酶在淋巴细胞中的高度调节表达为分析hTERT和hTER的转录调控贡献提供了机会。我们在这里报告的hTERT表达的分析北方和原位杂交。结果发现，hTERTmRNA的表达在可检测的水平，在所有的人淋巴细胞从胸腺，扁桃体和外周血中分离的子集，无论端粒酶活性的状态。hTERT表达作为谱系发育、分化和活化的功能被调节。然而，引人注目的是，这些细胞中的端粒酶活性与hTERT和hTER转录物的水平并不严格相关。端粒酶活性和hTERTmRNA之间的相关性的缺乏不能归因于hTERT剪接变体的存在或端粒酶活性的可检测的抑制剂。因此，hTERT的转录调控不足以解释人淋巴细胞中的端粒酶活性，表明转录后因子在控制酶功能中可能起作用。
Human telomerase consists of two essential components, telomerase RNA template (hTER) and telomerase reverse transcriptase (hTERT), and functions to synthesize telomere repeats that serve to protect the integrity of chromosomes and to prolong the replicative life span of cells. Telomerase activity is expressed selectively in germ-line and malignant tumor cells but not in most normal human somatic cells. As a notable exception, telomerase is expressed in human lymphocytes during development, differentiation, and activation. Recent studies have suggested that regulation of telomerase is determined by transcription of hTERT but not hTER. The highly regulated expression of telomerase in lymphocytes provides an opportunity to analyze the contribution of transcriptional regulation of hTERT and hTER. We report here an analysis of hTERT expression by Northern and ill situ hybridization. It was found that hTERT mRNA is expressed at detectable levels in all subsets of human lymphocytes isolated from thymus, tonsil, and peripheral blood, regardless of the status of telomerase activity. hTERT expression is regulated as a function of lineage development, differentiation, and activation. Strikingly, however, telomerase activity in these cells is not correlated strictly with the levels of hTERT and hTER transcripts. The absence of correlation between telomerase activity and hTERT mRNA could not be attributed to the presence of hTERT splice variants or to detectable inhibitors of telomerase activity. Thus, transcriptional regulation of hTERT is not sufficient to account for telomerase activity in human lymphocytes, indicating a likely role of posttranscriptional factors in the control of enzyme function.