Structural features of mouse telomerase RNA are responsible for the lower activity of mouse telomerase versus human telomerase
Structural features of mouse telomerase RNA are responsible for the lower activity of mouse telomerase versus human telomerase
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DOI：
10.1042/bj20060456
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发表时间：
2006-08-01
影响因子：
4.1
通讯作者：
Prasad, Vinayaka R.
中科院分区：
文献类型：
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作者：
Garforth, Scott J.;Wu, Yan Yun;Prasad, Vinayaka R.
人类和小鼠端粒酶在蛋白质和RNA成分上都显示出高度的相似性。人的端粒酶比老鼠的端粒酶更活跃，更具进行性。人的端粒酶RNA和小鼠的端粒酶结构之间有两个关键的区别。首先，小鼠端粒酶在其模板区的上游只含有2个核苷酸，而人类端粒酶含有45个核苷酸。其次，人端粒酶模板区含有5个核苷酸，而小鼠端粒酶模板区只有2个核苷酸。我们推测，这些差异是端粒酶活性差异的原因。HTR和MTR都发生了突变，改变了模板长度和模板上游RNA的长度，并利用体外翻译产生的小鼠端粒酶逆转录酶在体外重组了端粒酶。我们表明，模板区域上游的序列，与HTR中一样，有可能形成双链螺旋(P1螺旋)，增加端粒酶活性。更长的排列结构域只在PI螺旋的背景下增加端粒酶活性。因此，tr有助于调节哺乳动物端粒酶的活性水平。
Human and mouse telomerases show a high degree of similarity in both the protein and RNA components. Human telomerase is more active and more processive than the mouse telomerase. There are two key differences between hTR [human TR (telomerase RNA)] and mTR (mouse TR) structures. First, the mouse telomerase contains only 2 nt upstream of its template region, whereas the human telomerase contains 45 nt. Secondly, the template region of human telomerase contains a 5-nt alignment domain, whereas that of mouse has only 2 nt. We hypothesize that these differences are responsible for the differential telomerase activities. Mutations were made in both the hTR and mTR, changing the template length and the length of the RNA upstream of the template, and telomerase was reconstituted in vitro using mouse telomerase reverse transcriptase generated by in vitro translation. We show that the sequences upstream of the template region, with a potential to form a double-stranded helix (the P1 helix) as in hTR, increase telomerase activity. The longer alignment domain increases telomerase activity only in the context of the PI helix. Thus the TR contributes to regulating the level of activity of mammalian telomerases.