HEXIM1 targets a repeated GAUC motif in the riboregulator of transcription 7SK and promotes base pair rearrangements.
HEXIM1 targets a repeated GAUC motif in the riboregulator of transcription 7SK and promotes base pair rearrangements.
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DOI：
10.1093/nar/gkq660
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发表时间：
2010-11
影响因子：
14.9
通讯作者：
Dock-Bregeon AC
中科院分区：
文献类型：
--
作者：
Lebars I;Martinez-Zapien D;Durand A;Coutant J;Kieffer B;Dock-Bregeon AC
7SK snRNA是在人类细胞核中发现的一种丰富的RNA，通过RNA聚合酶II（RNAPII）调节转录。它隔离并抑制转录延伸因子P-TEFb，其通过RNAPII的磷酸化将转录从起始转换为进行性延伸并缓解转录的暂停。该调节过程依赖于7SK和HEXIM蛋白之间的结合，两种分离的伴侣都不能单独抑制P-TEFb。在这项工作中，我们使用了一种结合NMR和生物化学的方法来确定7SK和HEXIM 1元素，定义它们的结合特性。我们的研究结果表明，位于7SK 5′-端发夹上部的重复GAUC基序对于特异性HEXIM 1识别是必需的。包含HEXIM富含精氨酸基序（ARM）的肽的结合诱导GAUC基序的打开和内环的稳定化。一个保守的脯氨酸-丝氨酸序列的中间的ARM被证明是必不可少的结合特异性和构象变化的RNA。这项工作提供了证据的识别机制，涉及第一个事件的诱导适应，这表明7SK可塑性参与转录调控。
7SK snRNA, an abundant RNA discovered in human nucleus, regulates transcription by RNA polymerase II (RNAPII). It sequesters and inhibits the transcription elongation factor P-TEFb which, by phosphorylation of RNAPII, switches transcription from initiation to processive elongation and relieves pauses of transcription. This regulation process depends on the association between 7SK and a HEXIM protein, neither isolated partner being able to inhibit P-TEFb alone. In this work, we used a combined NMR and biochemical approach to determine 7SK and HEXIM1 elements that define their binding properties. Our results demonstrate that a repeated GAUC motif located in the upper part of a hairpin on the 5′-end of 7SK is essential for specific HEXIM1 recognition. Binding of a peptide comprising the HEXIM Arginine Rich Motif (ARM) induces an opening of the GAUC motif and stabilization of an internal loop. A conserved proline-serine sequence in the middle of the ARM is shown to be essential for the binding specificity and the conformational change of the RNA. This work provides evidences for a recognition mechanism involving a first event of induced fit, suggesting that 7SK plasticity is involved in the transcription regulation.
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影响因子：
3.9
作者：
Gruber, Andreas R.;Koper-Emde, Dorota;Marz, Manja;Tafer, Hakim;Bernhart, Stephan;Obernosterer, Gregor;Mosig, Axel;Hofacker, Ivo L.;Stadler, Peter F.;Benecke, Bernd-Joachim
通讯作者：
Benecke, Bernd-Joachim
影响因子：
11.4
作者：
Baumli, Sonja;Lolli, Graziano;Johnson, Louise N.
通讯作者：
Johnson, Louise N.
影响因子：
4.5
作者：
Hogg, J. Robert;Collins, Kathleen
通讯作者：
Collins, Kathleen
影响因子：
4.8
作者：
Dulac, C;Michels, AA;Bensaude, O
通讯作者：
Bensaude, O
影响因子：
16
作者：
He, Nanhai;Jahchan, Nadine S.;Zhou, Qiang
通讯作者：
Zhou, Qiang