A critical three-way junction is conserved in budding yeast and vertebrate telomerase RNAs.

A critical three-way junction is conserved in budding yeast and vertebrate telomerase RNAs.
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DOI:
10.1093/nar/gkm713
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发表时间:
2007
影响因子:
14.9
通讯作者:
Tzfati Y
Tzfati Y
中科院分区:
生物学2区
文献类型:
--
作者:
Brown Y;Abraham M;Pearl S;Kabaha MM;Elboher E;Tzfati Y

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端粒酶核糖核蛋白将其完整RNA部分内的短模板复制到真核细胞染色体末端,以补偿不完全复制和降解。端粒酶RNA的非模板区域(TER)对端粒酶功能也至关重要,但它们在物种间的序列高度不同,其作用在很大程度上不清楚。同时使用系统发育和突变分析,我们预测的TERs从克鲁维酵母芽殖酵母物种的二级结构。将这些二级结构模型与已发表的酿酒酵母TER模型进行比较,揭示了三条长臂的共同排列,中心有一个模板结构域,结构内相同位置有几个保守元件。其中之一,一个三向连接元件,是高度保守的芽殖酵母TER。该元件还显示出与脊椎动物TER的关键CR 4-CR 5活化结构域的序列和结构相似性。乳酸克鲁维酵母中的突变分析证实,该元件,特别是在酵母和脊椎动物中保守的残基,对于体内和体外的端粒酶作用都是至关重要的。这些发现表明,尽管来自不同生物体的TER序列存在极大差异,但它们确实共享保守元件,这些保守元件可能在端粒酶功能中发挥共同作用。
The telomerase ribonucleoprotein copies a short template within its integral RNA moiety onto eukaryotic chromosome ends, compensating for incomplete replication and degradation. Non-template regions of telomerase RNA (TER) are also crucial for telomerase function, yet they are highly divergent in sequence among species and their roles are largely unclear. Using both phylogenetic and mutational analyses, we predicted secondary structures for TERs from Kluyveromyces budding yeast species. A comparison of these secondary structure models with the published model for the Saccharomyces cerevisiae TER reveals a common arrangement into three long arms, a templating domain in the center and several conserved elements in the same positions within the structure. One of them, a three-way junction element, is highly conserved in budding yeast TERs. This element also shows sequence and structure similarity to the critical CR4-CR5 activating domain of vertebrate TERs. Mutational analysis in Kluyveromyces lactis confirmed that this element, and in particular the residues conserved across yeast and vertebrates, is critical for telomerase action both in vivo and in vitro. These findings demonstrate that despite the extreme divergence of TER sequences from different organisms, they do share conserved elements, which presumably carry out common roles in telomerase function.
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发表时间: 2007-07-10
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发表时间: 2006-01-01
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发表时间: 2006-07-12
期刊: EMBO JOURNAL
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