Human cells lacking coilin and Cajal bodies are proficient in telomerase assembly, trafficking and telomere maintenance.
Human cells lacking coilin and Cajal bodies are proficient in telomerase assembly, trafficking and telomere maintenance.
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缺乏线圈蛋白和卡哈尔小体的人体细胞精通端粒酶组装、运输和端粒维持
DOI：
10.1093/nar/gku1277
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发表时间：
2015-01
影响因子：
14.9
通讯作者：
Zhao Y
中科院分区：
文献类型：
--
作者：
Chen Y;Deng Z;Jiang S;Hu Q;Liu H;Songyang Z;Ma W;Chen S;Zhao Y
人端粒酶（human telomerase，hTR）的RNA组分定位于Cajal小体，Cajal小体在端粒酶全酶的组装和端粒酶的运输中起重要作用。在此，在缺乏卷曲蛋白的人细胞（即卷曲蛋白敲除（KO）细胞）中检查了Cajal小体的作用，其中未检测到Cajal小体。在coilin-KO细胞中，检测到正常水平的端粒酶活性，并且全酶的核心因子之间的相互作用得以保留，表明端粒酶组装在Cajal小体不存在的情况下发生。此外，分散的hTR聚集并在卷曲蛋白KO细胞中特异性地在S和G2期形成灶。这些hTR灶与端粒的共定位意味着适当的端粒酶贩运，独立于卡哈尔小体。因此，端粒酶在卷曲蛋白-KO和对照细胞中向端粒添加相似数量的TTAGGG重复。过表达TPP 1-OB-折叠阻断细胞周期依赖性hTR灶的形成并抑制端粒延伸。这些发现表明，端粒酶组装，运输和延伸发生在正常效率的卡哈尔体缺陷的人类细胞。因此，Cajal小体本身在这些过程中不是必需的，尽管Cajal小体的非卷曲蛋白组分和/或端粒结合蛋白（例如TPP 1）在端粒酶生物发生和端粒稳态中发挥作用仍然是可能的。
The RNA component of human telomerase (hTR) localizes to Cajal bodies, and it has been proposed that Cajal bodies play a role in the assembly of telomerase holoenzyme and telomerase trafficking. Here, the role of Cajal bodies was examined in Human cells deficient of coilin (i.e. coilin-knockout (KO) cells), in which no Cajal bodies are detected. In coilin-KO cells, a normal level of telomerase activity is detected and interactions between core factors of holoenzyme are preserved, indicating that telomerase assembly occurs in the absence of Cajal bodies. Moreover, dispersed hTR aggregates and forms foci specifically during S and G2 phase in coilin-KO cells. Colocalization of these hTR foci with telomeres implies proper telomerase trafficking, independent of Cajal bodies. Therefore, telomerase adds similar numbers of TTAGGG repeats to telomeres in coilin-KO and controls cells. Overexpression of TPP1-OB-fold blocks cell cycle-dependent formation of hTR foci and inhibits telomere extension. These findings suggest that telomerase assembly, trafficking and extension occur with normal efficiency in Cajal bodies deficient human cells. Thus, Cajal bodies, as such, are not essential in these processes, although it remains possible that non-coilin components of Cajal bodies and/or telomere binding proteins (e.g. TPP1) do play roles in telomerase biogenesis and telomere homeostasis.
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端粒蛋白TPP1的TEL斑块介导端粒酶募集和加工性。
影响因子：
64.8
作者：
通讯作者：
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影响因子：
3.3
作者：
Deryusheva, Svetlana;Gall, Joseph G.
通讯作者：
Gall, Joseph G.
影响因子：
3.3
作者：
Liu, Ji-Long;Wu, Zheng'an;Gall, Joseph G.
通讯作者：
Gall, Joseph G.
影响因子：
3.3
作者：
Tomlinson, RL;Ziegler, TD;Terns, MP
通讯作者：
Terns, MP
影响因子：
5.3
作者：
Stern, J. Lewis;Zyner, Katherine G.;Bryan, Tracy M.
通讯作者：
Bryan, Tracy M.