The RNA accordion model for template positioning by telomerase RNA during telomeric DNA synthesis.

The RNA accordion model for template positioning by telomerase RNA during telomeric DNA synthesis.
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端粒DNA合成过程中端粒酶RNA定位的RNA手风琴模型。

DOI:
10.1038/nsmb.2174
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发表时间:
2011-11-20
影响因子:
16.8
通讯作者:
Cech, Thomas R.
Cech, Thomas R.
中科院分区:
生物学1区
文献类型:
--
作者:
Berman, Andrea J.;Akiyama, Benjamin M.;Stone, Michael D.;Cech, Thomas R.

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端粒酶是一种核糖核蛋白(RNP)酶,维持真核生物线性染色体的末端,其激活是90%的癌症的标志。这个RNP最低限度地包含一个催化端粒DNA合成的逆转录酶蛋白质亚单位(TERT)和一个具有模板、建筑和蛋白质支架作用的RNA亚单位(TER)。端粒酶在聚合酶中是独一无二的,因为它在单一结合事件后在引物的3‘端合成模板的多个副本,这一过程被称为重复加成过程(RAP)。通过对嗜热四膜虫端粒酶的生化分析和单分子Förster共振能量转移(SmFRET)实验,我们现在直接证明了TER有助于RAP所需的模板定位和模板移位。我们认为模板两侧的单链RNA元件起到了分子手风琴的作用,在端粒酶易位过程中经历了相互伸展和紧凑。
Telomerase is a ribonucleoprotein (RNP) enzyme that maintains the ends of linear eukaryotic chromosomes and whose activation is a hallmark of 90% of all cancers. This RNP minimally contains a reverse transcriptase protein subunit (TERT) that catalyzes telomeric DNA synthesis and an RNA subunit (TER) that has templating, architectural and protein-scaffolding roles. Telomerase is unique among polymerases in that it synthesizes multiple copies of the template on the 3′ end of a primer following a single binding event, a process known as repeat addition processivity (RAP). Using biochemical assays and single-molecule Förster resonance energy transfer (smFRET) experiments on Tetrahymena thermophila telomerase, we now directly demonstrate that TER contributes to template positioning within the active site and to the template translocation required for RAP. We propose that the single-stranded RNA elements flanking the template act as a molecular accordion, undergoing reciprocal extension and compaction during telomerase translocation.
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