A three-state model for the regulation of telomerase by TERRA and hnRNPA1.
A three-state model for the regulation of telomerase by TERRA and hnRNPA1.
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DOI：
10.1093/nar/gkt695
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发表时间：
2013-10
影响因子：
14.9
通讯作者：
Lingner J
中科院分区：
文献类型：
--
作者：
Redon S;Zemp I;Lingner J
端粒是真核细胞染色体的物理末端，被转录成端粒重复序列RNA(Terra)，这是一种大的非编码RNA，构成了端粒异染色质的组成部分。在体外，裸露的Terra分子是有效的人类端粒酶抑制剂，除了与端粒酶逆转录酶蛋白亚基接触外，还通过其5‘-UUAGGG-3’重复序列与端粒酶RNA的模板序列进行碱基配对。然而，在体内，Terra介导的端粒酶抑制可以通过未知的机制来阻止。此外，异质性核核糖核蛋白A1(HnRNPA1)也参与了端粒长度的控制。在体内，Terra部分与hnRNPA1相关，hnRNPA1也在端粒上检测到。我们证明，在与Terra结合时，hnRNPA1可以缓解Terra介导的端粒酶抑制。然而，当超过Terra时，hnRNPA1本身就成为端粒延伸的抑制剂，与端粒DNA底物结合。然而，hnRNPA1对端粒酶的催化没有显著的直接作用。我们的体外结果表明，在体内，hnRNPA1可能阻止Terra介导的端粒酶抑制。端粒酶的端粒延伸可能需要端粒上Terra和hnRNPA1的平衡水平。因此，Terra和hnRNPA1可以作为双分子调节器来启动和关闭端粒酶和端粒。
Telomeres, the physical ends of eukaryotic chromosomes, are transcribed into telomeric repeat-containing RNA (TERRA), a large non-coding RNA, which forms an integral part of telomeric heterochromatin. In vitro, naked TERRA molecules are efficient inhibitors of human telomerase, base-pairing via their 5′-UUAGGG-3′ repeats with the template sequence of telomerase RNA, in addition to contacting the telomerase reverse transcriptase protein subunit. In vivo, however, TERRA-mediated inhibition of telomerase can be prevented by unknown mechanisms. Also, heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) has been implicated in telomere length control. In vivo, TERRA is partially associated with hnRNPA1, and hnRNPA1 is also detected at telomeres. We demonstrate that on binding of TERRA, hnRNPA1 can alleviate the TERRA-mediated inhibition of telomerase. However, when in excess over TERRA, hnRNPA1 becomes itself an inhibitor of telomere extension, on binding of the telomeric DNA substrate. Yet, hnRNPA1 has no notable direct effects on the telomerase catalysis. Our in vitro results suggest that TERRA-mediated telomerase inhibition may be prevented by hnRNPA1 in vivo. Telomere extension by telomerase may require balanced levels of TERRA and hnRNPA1 at telomeres. Thus, TERRA and hnRNPA1 can function as a bimolecular regulator to turn telomerase and the telomere on and off.
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影响因子：
4.5
作者：
Pfeiffer V;Lingner J
通讯作者：
Lingner J
DOI：
10.1126/science.1170633
发表时间：
2009-11-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
de Lange T
通讯作者：
de Lange T
影响因子：
64.8
作者：
Chen, Liuh-Yow;Redon, Sophie;Lingner, Joachim
通讯作者：
Lingner, Joachim
影响因子：
5.3
作者：
Porro, Antonio;Feuerhahn, Sascha;Lingner, Joachim
通讯作者：
Lingner, Joachim
影响因子：
5.3
作者：
ISHIKAWA, F;MATUNIS, MJ;CECH, TR
通讯作者：
CECH, TR