ATP-independent diffusion of double-stranded RNA binding proteins
ATP-independent diffusion of double-stranded RNA binding proteins
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DOI：
10.1073/pnas.1212917110
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发表时间：
2013-01-02
影响因子：
11.1
通讯作者：
Myong, Sua
中科院分区：
文献类型：
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作者：
Koh, Hye Ran;Kidwell, Mary Anne;Myong, Sua
含有双链RNA结合结构域（dsRBD）的蛋白质在RNA定位、剪接、编辑、输出和翻译等方面发挥着多种功能，但其作用机制和功能意义尚不清楚。为了解开这个谜，我们研究了由三个dsRBD组成的反式激活反应RNA结合蛋白（TRBP），其在HIV复制、蛋白激酶R（PKR）介导的免疫反应和RNA沉默中发挥作用。在这里，我们报告了一个ATP-独立的扩散活动TRBP专门对dsRNA的长度依赖性的方式。TRBP的前两个dsRBD对于扩散是必不可少的，而第三个dsRBD是双链的。TRBP的两个同源物PKR activator和R3 D1-L显示了相同的扩散，这意味着该蛋白家族中扩散活性的普遍性。此外，双链RNA上的Dicer-TRBP复合物表现出动态扩散，这与Dicer的催化活性相关。这些结果表明TRBP的dsRNA特异性扩散活性有助于增强Dicer对siRNA和miRNA的加工。
The proteins harboring double-stranded RNA binding domains (dsRBDs) play diverse functional roles such as RNA localization, splicing, editing, export, and translation, yet mechanistic basis and functional significance of dsRBDs remain unclear. To unravel this enigma, we investigated transactivation response RNA binding protein (TRBP) consisting of three dsRBDs, which functions in HIV replication, protein kinase R(PKR)-mediated immune response, and RNA silencing. Here we report an ATP-independent diffusion activity of TRBP exclusively on dsRNA in a length-dependent manner. The first two dsRBDs of TRBP are essential for diffusion, whereas the third dsRBD is dispensable. Two homologs of TRBP, PKR activator and R3D1-L, displayed the same diffusion, implying a universality of the diffusion activity among this protein family. Furthermore, a Dicer-TRBP complex on dsRNA exhibited dynamic diffusion, which was correlated with Dicer's catalytic activity. These results implicate the dsRNA-specific diffusion activity of TRBP that contributes to enhancing siRNA and miRNA processing by Dicer.