The Drosophila 7SK snRNP and the essential role of dHEXIM in development.
The Drosophila 7SK snRNP and the essential role of dHEXIM in development.
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DOI：
10.1093/nar/gks191
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发表时间：
2012-07
影响因子：
14.9
通讯作者：
Price DH
中科院分区：
文献类型：
--
作者：
Nguyen D;Krueger BJ;Sedore SC;Brogie JE;Rogers JT;Rajendra TK;Saunders A;Matera AG;Lis JT;Uguen P;Price DH
正转录延伸因子P-TEFb的调节在控制哺乳动物转录中起主要作用，这部分是通过从7SK snRNP中控制释放P-TEFb来实现的，7SK snRNP将激酶隔离在非活性状态。我们在这里证明，一个类似的P-TEFb控制系统存在于果蝇。我们表明，以前被认为是一个7SK同源物的RNA，事实上，与P-TEFb，通过人类HEXIM 1/2蛋白（dHEXIM）的同源物的作用。此外，果蝇La相关蛋白（现在称为dLARP 7）被证明是人类LARP 7的功能同源物。果蝇7SK snRNP（d 7SK snRNP）对用P-TEFb抑制剂处理细胞和通过释放P-TEFb对细胞裂解物的核酸酶处理作出响应。支持d 7SK snRNP在果蝇发育中的关键作用，发现dLARP 7和dHEXIM在所有阶段的胚胎和组织中普遍表达。重要的是，dHEXIM的敲低是胚胎致死的，并且特定组织中dHEXIM的减少导致严重的发育缺陷。我们的研究结果表明，调节P-TEFb的d 7SK snRNP是必不可少的果蝇发育过程中所需的组织的生长和分化。
Regulation of the positive transcription elongation factor, P-TEFb, plays a major role in controlling mammalian transcription and this is accomplished in part by controlled release of P-TEFb from the 7SK snRNP that sequesters the kinase in an inactive state. We demonstrate here that a similar P-TEFb control system exists in Drosophila. We show that an RNA previously suggested to be a 7SK homolog is, in fact, associated with P-TEFb, through the action of a homolog of the human HEXIM1/2 proteins (dHEXIM). In addition, a Drosophila La related protein (now called dLARP7) is shown to be the functional homolog of human LARP7. The Drosophila 7SK snRNP (d7SK snRNP) responded to treatment of cells with P-TEFb inhibitors and to nuclease treatment of cell lysates by releasing P-TEFb. Supporting a critical role for the d7SK snRNP in Drosophila development, dLARP7 and dHEXIM were found to be ubiquitously expressed throughout embryos and tissues at all stages. Importantly, knockdown of dHEXIM was embryonic lethal, and reduction of dHEXIM in specific tissues led to serious developmental defects. Our results suggest that regulation of P-TEFb by the d7SK snRNP is essential for the growth and differentiation of tissues required during Drosophila development.
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影响因子：
3.7
作者：
Krueger BJ;Varzavand K;Cooper JJ;Price DH
通讯作者：
Price DH
影响因子：
64.5
作者：
Levine M
通讯作者：
Levine M
DOI：
10.1016/j.cub.2009.02.055
发表时间：
2009-04-28
期刊：
Current biology : CB
影响因子：
--
作者：
Chopra VS;Hong JW;Levine M
通讯作者：
Levine M
影响因子：
14.9
作者：
Li Q;Cooper JJ;Altwerger GH;Feldkamp MD;Shea MA;Price DH
通讯作者：
Price DH
影响因子：
64.5
作者：
Guenther, Matthew G.;Levine, Stuart S.;Young, Richard A.
通讯作者：
Young, Richard A.