Greenberg R A, Allsopp R C, Chin L, Morin G B, DePinho R A
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Oncogene. 1998 Apr 2;16(13):1723-30. doi: 10.1038/sj.onc.1201933.
We have identified the mouse telomerase reverse transcriptase component (mTERT) and demonstrate both substantial sequence homology to the human ortholog (hTERT), and the presence of reverse transcriptase and telomerase specific motifs. Furthermore, we show functional interchangeability with hTERT in in vitro telomerase reconstitution experiments, as mTERT produces strong telomerase activity in combination with the human telomerase RNA component hTR. The mouse TERT is widely expressed at low levels in adult tissues, with greatest abundance during embryogenesis and in adult thymus and intestine. The mTERT component mRNA levels were regulated during both differentiation and proliferation, while mTR levels remained constant throughout both processes. Comparison of mTERT and mTR levels to telomerase activity indicates that mTERT expression is more tightly linked to the regulation of telomerase activity during these processes than is mTR. In contrast to the situation in human cell cultures, mTERT transcript levels are present at readily detectable levels in primary cultured cells and are not upregulated following crisis. The widespread expression of mTERT in primary cells and mouse tissues could explain the increased frequency of spontaneous immortalization of mouse cells in culture and tumorigenesis in vivo.
我们已经鉴定出小鼠端粒酶逆转录酶组分(mTERT),并证明其与人类直系同源物(hTERT)具有高度的序列同源性,且存在逆转录酶和端粒酶特异性基序。此外,在体外端粒酶重建实验中,我们发现mTERT与hTERT具有功能互换性,因为mTERT与人类端粒酶RNA组分hTR结合时能产生强大的端粒酶活性。小鼠TERT在成年组织中广泛低水平表达,在胚胎发育期间以及成年胸腺和肠道中表达量最高。mTERT组分的mRNA水平在分化和增殖过程中均受到调控,而mTR水平在这两个过程中保持恒定。将mTERT和mTR水平与端粒酶活性进行比较表明,在这些过程中,mTERT的表达比mTR与端粒酶活性的调控联系更为紧密。与人类细胞培养的情况不同,mTERT转录本水平在原代培养细胞中易于检测到,并且在危机后不会上调。mTERT在原代细胞和小鼠组织中的广泛表达可以解释培养的小鼠细胞自发永生化频率增加以及体内肿瘤发生的现象。