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

ABSTRACT: 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.

SUBMITTER: Ozdilek BA

PROVIDER: S-EPMC5570134 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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

Ozdilek Bagdeser A BA Thompson Valery F VF Ahmed Nasiha S NS White Connor I CI Batey Robert T RT Schwartz Jacob C JC

Nucleic acids research 20170701 13

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 fol ...[more]

PMID: 28575444

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