S6K2-mediated regulation of TRBP as a determinant of miRNA expression in human primary lymphatic endothelial cells.
S6K2-mediated regulation of TRBP as a determinant of miRNA expression in human primary lymphatic endothelial cells.
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DOI：
10.1093/nar/gkw631
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发表时间：
2016-11-16
影响因子：
14.9
通讯作者：
Lagos D
中科院分区：
文献类型：
--
作者：
Warner MJ;Bridge KS;Hewitson JP;Hodgkinson MR;Heyam A;Massa BC;Haslam JC;Chatzifrangkeskou M;Evans GJ;Plevin MJ;Sharp TV;Lagos D
MicroRNAs(MiRNAs)是一种使mRNAs沉默的非编码短小RNA。它们是在DROSHA/DgCr8和Dird/TRBP/PACT复合体转录和切割后产生的。虽然已知miRNA生物发生机制的组成部分可以被磷酸化，但这些事件是如何在生理细胞激活过程中参与的仍然知之甚少。我们证明S6激酶可以磷酸化TRBP的扩展的C-末端结构域，并在原代细胞中与TRBP原位相互作用。TRBP丝氨酸283/286对于S6K介导的TRBP磷酸化、TRBP的最佳表达以及S6K-TRBP在人原代细胞中的相互作用是必不可少的。我们证明了这种相互作用在原代人皮肤淋巴管内皮细胞(HDLECs)中的功能相关性。血管生成素-1(Angiopoietin-1，Ang1)可通过S6K2依赖的方式促进TRBP的磷酸化和表达，从而增强HDLEC的miRNA生物合成。我们认为S6K2/TRBP节点控制着HDLECs中miRNA的生物发生，并在mTOR途径和miRNA生物发生机制之间提供了分子联系。
MicroRNAs (miRNAs) are short non-coding RNAs that silence mRNAs. They are generated following transcription and cleavage by the DROSHA/DGCR8 and DICER/TRBP/PACT complexes. Although it is known that components of the miRNA biogenesis machinery can be phosphorylated, it remains poorly understood how these events become engaged during physiological cellular activation. We demonstrate that S6 kinases can phosphorylate the extended C-terminal domain of TRBP and interact with TRBP in situ in primary cells. TRBP serines 283/286 are essential for S6K-mediated TRBP phosphorylation, optimal expression of TRBP, and the S6K-TRBP interaction in human primary cells. We demonstrate the functional relevance of this interaction in primary human dermal lymphatic endothelial cells (HDLECs). Angiopoietin-1 (ANG1) can augment miRNA biogenesis in HDLECs through enhancing TRBP phosphorylation and expression in an S6K2-dependent manner. We propose that the S6K2/TRBP node controls miRNA biogenesis in HDLECs and provides a molecular link between the mTOR pathway and the miRNA biogenesis machinery.
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DOI：
10.1152/ajpheart.01081.2005
发表时间：
2006-10-01
影响因子：
4.8
作者：
Chen, Jian-Xiong;Zeng, Heng;Meyrick, Barbara
通讯作者：
Meyrick, Barbara
影响因子：
20.1
作者：
Kuehbacher, Angelika;Urbich, Carmen;Dimmeler, Stefanie
通讯作者：
Dimmeler, Stefanie
影响因子：
16
作者：
Horman, Shane R.;Janas, Maja M.;Litterst, Claudia;Wang, Bingbing;MacRae, Ian J.;Sever, Mary J.;Morrissey, David V.;Graves, Paul;Luo, Biao;Umesalma, Shaikamjad;Qi, Hank H.;Miraglia, Loren J.;Novina, Carl D.;Orth, Anthony P.
通讯作者：
Orth, Anthony P.
影响因子：
21.3
作者：
Liu, Pengda;Gan, Wenjian;Inuzuka, Hiroyuki;Lazorchak, Adam S.;Gao, Daming;Arojo, Omotooke;Liu, Dou;Wan, Lixin;Zhai, Bo;Yu, Yonghao;Yuan, Min;Kim, Byeong Mo;Shaik, Shavali;Menon, Suchithra;Gygi, Steven P.;Lee, Tae Ho;Asara, John M.;Manning, Brendan D.;Blenis, John;Su, Bing;Wei, Wenyi
通讯作者：
Wei, Wenyi
影响因子：
30.3
作者：
Lagos D;Vart RJ;Gratrix F;Westrop SJ;Emuss V;Wong PP;Robey R;Imami N;Bower M;Gotch F;Boshoff C
通讯作者：
Boshoff C