The conserved structure of plant telomerase RNA provides the missing link for an evolutionary pathway from ciliates to humans

The conserved structure of plant telomerase RNA provides the missing link for an evolutionary pathway from ciliates to humans
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植物端粒酶RNA的保守结构为从纤毛虫到人类的进化途径提供了缺失的一环

DOI:
10.1073/pnas.1915312116
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发表时间:
2019
期刊:
Proceedings of the National Academy of Sciences
影响因子:
--
通讯作者:
Shippen, Dorothy E.
Shippen, Dorothy E.
中科院分区:
--
文献类型:
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作者:
Song, Jiarui;Logeswaran, Dhenugen;Castillo-González, Claudia;Li, Yang;Bose, Sreyashree;Aklilu, Behailu Birhanu;Ma, Zeyang;Polkhovskiy, Alexander;Chen, Julian J.-L.;Shippen, Dorothy E.

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端粒酶对维持端粒的完整性至关重要。虽然端粒酶的功能是广泛保守的,但为端粒DNA合成提供模板的端粒酶RNA(TR)已经发生了显着的分化。然而,TR分子保留2个高度保守的结构域催化的关键:模板近端假结(PK)结构和下游茎环结构。在这里,我们介绍了真正的TR从植物拟南芥,称为AtTR,确定通过下一代测序的RNA copurifying与拟南芥的TERT。这种RNA不同于先前描述为模板端粒酶RNA AtTER 1的RNA。AtTR是一种268-nt的Pol III转录物,在体内维持端粒是必需的,在体外与TERT一起足以重建端粒酶活性。生物信息学分析从被子植物、裸子植物和石松植物3个主要分支中鉴定出85个AtTR同源基因。通过系统发育比较,推断并验证了一个二级结构模型之间的植物TR保守的体外和体内化学探针。保守的植物TR结构包含一个由P1茎和3′长茎P4/5/6包围的模板PK核心结构域,这两个结构域类似于纤毛虫和脊椎动物TR中相应的结构元件。然而,植物TR包含额外的茎和连接器内的模板PK核心,允许扩展的PK结构从简单的PK在较小的纤毛虫TR在进化过程中。因此,植物TR提供了一个进化的桥梁,统一了不同的结构,以前表征的TR从纤毛虫和脊椎动物。
Telomerase is essential for maintaining telomere integrity. Although telomerase function is widely conserved, the integral telomerase RNA (TR) that provides a template for telomeric DNA synthesis has diverged dramatically. Nevertheless, TR molecules retain 2 highly conserved structural domains critical for catalysis: a template-proximal pseudoknot (PK) structure and a downstream stem-loop structure. Here we introduce the authentic TR from the plantArabidopsis thaliana, called AtTR, identified through next-generation sequencing of RNAs copurifying withArabidopsisTERT. This RNA is distinct from the RNA previously described as the templating telomerase RNA, AtTER1. AtTR is a 268-nt Pol III transcript necessary for telomere maintenance in vivo and sufficient with TERT to reconstitute telomerase activity in vitro. Bioinformatics analysis identified 85 AtTR orthologs from 3 major clades of plants: angiosperms, gymnosperms, and lycophytes. Through phylogenetic comparisons, a secondary structure model conserved among plant TRs was inferred and verified using in vitro and in vivo chemical probing. The conserved plant TR structure contains a template-PK core domain enclosed by a P1 stem and a 3′ long-stem P4/5/6, both of which resemble a corresponding structural element in ciliate and vertebrate TRs. However, the plant TR contains additional stems and linkers within the template-PK core, allowing for expansion of PK structure from the simple PK in the smaller ciliate TR during evolution. Thus, the plant TR provides an evolutionary bridge that unites the disparate structures of previously characterized TRs from ciliates and vertebrates.
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