Role of the amino terminal RHAU-specific motif in the recognition and resolution of guanine quadruplex-RNA by the DEAH-box RNA helicase RHAU.
Role of the amino terminal RHAU-specific motif in the recognition and resolution of guanine quadruplex-RNA by the DEAH-box RNA helicase RHAU.
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DOI：
10.1093/nar/gkq372
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发表时间：
2010-10
影响因子：
14.9
通讯作者：
Nagamine Y
中科院分区：
文献类型：
--
作者：
Lattmann S;Giri B;Vaughn JP;Akman SA;Nagamine Y
在生理条件下，富含鸟嘌呤的DNA和RNA序列可以采用稳定的非典型四链螺旋结构，称为g -四联体（G4）。这种G4结构已被证明存在于体内，并在转录、翻译和端粒维护等多种过程中发挥作用。由于其高热力学稳定性，G4结构在体内的分解需要专门的酶。RHAU是DEAH-box家族的一种人类RNA解旋酶，在体外对其底物具有高亲和力和特异性，具有独特的atp依赖性g4分解活性。RHAU如何识别g4 - rna尚未确定。在这里，我们发现了RHAU的氨基末端区域是RHAU结合G4结构所必需的，并进一步确定了在该区域内进化保守的RSM （RHAU特异性基序）结构域是主要的亲和力和特异性决定因素。在RSM是其唯一保守基序的氨基末端区域，果蝇同源物CG9323也具有g4分解活性和严格的RSM依赖性。因此，这些结果揭示了RHAU蛋白中一个新的基序，在识别和解析G4-RNA结构中起重要作用，这是许多已知RNA解旋酶中RHAU所独有的特性。
Under physiological conditions, guanine-rich sequences of DNA and RNA can adopt stable and atypical four-stranded helical structures called G-quadruplexes (G4). Such G4 structures have been shown to occur in vivo and to play a role in various processes such as transcription, translation and telomere maintenance. Owing to their high-thermodynamic stability, resolution of G4 structures in vivo requires specialized enzymes. RHAU is a human RNA helicase of the DEAH-box family that exhibits a unique ATP-dependent G4-resolvase activity with a high affinity and specificity for its substrate in vitro. How RHAU recognizes G4-RNAs has not yet been established. Here, we show that the amino-terminal region of RHAU is essential for RHAU to bind G4 structures and further identify within this region the evolutionary conserved RSM (RHAU-specific motif) domain as a major affinity and specificity determinant. G4-resolvase activity and strict RSM dependency are also observed with CG9323, the Drosophila orthologue of RHAU, in the amino terminal region of which the RSM is the only conserved motif. Thus, these results reveal a novel motif in RHAU protein that plays an important role in recognizing and resolving G4-RNA structures, properties unique to RHAU among many known RNA helicases.
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影响因子：
14.9
作者：
Cole C;Barber JD;Barton GJ
通讯作者：
Barton GJ
DOI：
10.1074/jbc.c900018200
发表时间：
2009-04-17
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Collins R;Karlberg T;Lehtiö L;Schütz P;van den Berg S;Dahlgren LG;Hammarström M;Weigelt J;Schüler H
通讯作者：
Schüler H
影响因子：
5.7
作者：
Kim, JL;Morgenstern, KA;Caron, PR
通讯作者：
Caron, PR
影响因子：
2.9
作者：
Grohman, Jacob K.;Del Campo, Mark;Russell, Rick
通讯作者：
Russell, Rick
影响因子：
4.8
作者：
Karginov, FV;Caruthers, JM;Uhlenbeck, OC
通讯作者：
Uhlenbeck, OC