A human telomerase holoenzyme protein required for Cajal body localization and telomere synthesis.

A human telomerase holoenzyme protein required for Cajal body localization and telomere synthesis.
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DOI:
10.1126/science.1165357
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发表时间:
2009-01-30
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Artandi SE
Artandi SE
中科院分区:
其他
文献类型:
--
作者:
Venteicher AS;Abreu EB;Meng Z;McCann KE;Terns RM;Veenstra TD;Terns MP;Artandi SE

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端粒酶是在组织祖细胞和癌细胞中合成端粒重复序列的核糖核蛋白(RNP)复合体。活跃的人类端粒酶至少由三个主要亚基组成,包括端粒酶逆转录酶(TERT)、端粒酶RNA (TERC)和dyskerin。在这里,我们确定了一个全酶亚基,TCAB1(端粒酶Cajal体蛋白1),独特地富集于Cajal体,RNP加工的核位点对端粒酶功能很重要。TCAB1与活性端粒酶、已建立的端粒酶组分以及参与修饰剪接rna的Cajal小体rna相关。利用RNA干扰去除TCAB1可阻止TERC与Cajal小体结合,破坏端粒酶-端粒结合,并消除端粒酶合成端粒。因此,TCAB1控制端粒酶运输,是人类癌细胞端粒合成所必需的。
Telomerase is a ribonucleoprotein (RNP) complex that synthesizes telomere repeats in tissue progenitor cells and cancer cells. Active human telomerase consists of at least three principal subunits, including the telomerase reverse transcriptase (TERT), the telomerase RNA (TERC), and dyskerin. Here, we identify a holoenzyme subunit, TCAB1 (telomerase Cajal body protein1), uniquely enriched in Cajal bodies, nuclear sites of RNP processing important for telomerase function. TCAB1 associates with active telomerase enzyme, with established telomerase components, and with small Cajal body RNAs involved in modifying splicing RNAs. Depletion of TCAB1 using RNA interference prevents TERC from associating with Cajal bodies, disrupts telomerase-telomere association and abrogates telomere synthesis by telomerase. Thus, TCAB1 controls telomerase trafficking and is required for telomere synthesis in human cancer cells.
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