Intrinsically disordered RGG/RG domains mediate degenerate specificity in RNA binding.

Intrinsically disordered RGG/RG domains mediate degenerate specificity in RNA binding.
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本质上无序的RGG/RG结构域介导了RNA结合中的退化特异性。

DOI:
10.1093/nar/gkx460
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发表时间:
2017-07-27
影响因子:
14.9
通讯作者:
Schwartz JC
Schwartz JC
中科院分区:
生物学2区
文献类型:
--
作者:
Ozdilek BA;Thompson VF;Ahmed NS;White CI;Batey RT;Schwartz JC

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RGG/RG结构域是人类基因组中第二常见的RNA结合结构域,但其RNA结合特性仍然知之甚少。在这里,我们报告了融合肉瘤(FUS),FMRP和hnRNPU的内在无序RGG/RG结构域的RNA结合特性的详细分析。对于FUS,以前的研究定义RNA结合介导的折叠结构域,然而,我们发现,RGG/RG结构域是主要的介质结合。与相邻折叠结构域偶联的RGG/RG结构域可以实现接近全长FUS的亲和力。对来自FUS、FMRP和hnRNPU的RGG/RG结构域针对对比RNA的光谱的分析揭示,每个显示简并结合特异性,同时仍然显示对RNA的不同程度的偏好。
RGG/RG domains are the second most common RNA binding domain in the human genome, yet their RNA-binding properties remain poorly understood. Here, we report a detailed analysis of the RNA binding characteristics of intrinsically disordered RGG/RG domains from Fused in Sarcoma (FUS), FMRP and hnRNPU. For FUS, previous studies defined RNA binding as mediated by its well-folded domains; however, we show that RGG/RG domains are the primary mediators of binding. RGG/RG domains coupled to adjacent folded domains can achieve affinities approaching that of full-length FUS. Analysis of RGG/RG domains from FUS, FMRP and hnRNPU against a spectrum of contrasting RNAs reveals that each display degenerate binding specificity, while still displaying different degrees of preference for RNA.
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