端粒酶RNA茎端元件影响模板边界元件功能、端粒序列和端粒保护蛋白结合。
Telomerase RNA stem terminus element affects template boundary element function, telomere sequence, and shelterin binding.
作者信息
Webb Christopher J, Zakian Virginia A
机构信息
Department of Molecular Biology, Princeton University, Princeton, NJ 08544.
Department of Molecular Biology, Princeton University, Princeton, NJ 08544
出版信息
Proc Natl Acad Sci U S A. 2015 Sep 8;112(36):11312-7. doi: 10.1073/pnas.1503157112. Epub 2015 Aug 24.
The stem terminus element (STE), which was discovered 13 y ago in human telomerase RNA, is required for telomerase activity, yet its mode of action is unknown. We report that the Schizosaccharomyces pombe telomerase RNA, TER1 (telomerase RNA 1), also contains a STE, which is essential for telomere maintenance. Cells expressing a partial loss-of-function TER1 STE allele maintained short stable telomeres by a recombination-independent mechanism. Remarkably, the mutant telomere sequence was different from that of wild-type cells. Generation of the altered sequence is explained by reverse transcription into the template boundary element, demonstrating that the STE helps maintain template boundary element function. The altered telomeres bound less Pot1 (protection of telomeres 1) and Taz1 (telomere-associated in Schizosaccharomyces pombe 1) in vivo. Thus, the S. pombe STE, although distant from the template, ensures proper telomere sequence, which in turn promotes proper assembly of the shelterin complex.
茎端末端元件（STE）于13年前在人端粒酶RNA中被发现，它是端粒酶活性所必需的，但其作用方式尚不清楚。我们报道，粟酒裂殖酵母端粒酶RNA（TER1，端粒酶RNA1）也含有一个STE，这对端粒维持至关重要。表达部分功能丧失的TER1 STE等位基因的细胞通过一种不依赖重组的机制维持短而稳定的端粒。值得注意的是，突变的端粒序列与野生型细胞的不同。序列改变的产生可通过逆转录进入模板边界元件来解释，这表明STE有助于维持模板边界元件的功能。改变后的端粒在体内与较少的Pot1（端粒保护蛋白1）和Taz1（粟酒裂殖酵母端粒相关蛋白1）结合。因此，粟酒裂殖酵母的STE虽然远离模板，但能确保端粒序列正确，进而促进端粒保护蛋白复合体的正确组装。
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