The Drosophila hnRNP F/H Homolog Glorund Uses Two Distinct RNA-Binding Modes to Diversify Target Recognition

Publication date: 4 April 2017
Source:Cell Reports, Volume 19, Issue 1
Author(s): Joel V. Tamayo, Takamasa Teramoto, Seema Chatterjee, Traci M. Tanaka Hall, Elizabeth R. Gavis
The Drosophila hnRNP F/H homolog, Glorund (Glo), regulates nanos mRNA translation by interacting with a structured UA-rich motif in the nanos 3′ untranslated region. Glo regulates additional RNAs, however, and mammalian homologs bind G-tract sequences to regulate alternative splicing, suggesting that Glo also recognizes G-tract RNA. To gain insight into how Glo recognizes both structured UA-rich and G-tract RNAs, we used mutational analysis guided by crystal structures of Glo's RNA-binding domains and identified two discrete RNA-binding surfaces that allow Glo to recognize both RNA motifs. By engineering Glo variants that favor a single RNA-binding mode, we show that a subset of Glo's functions in vivo is mediated solely by the G-tract binding mode, whereas regulation of nanos requires both recognition modes. Our findings suggest a molecular mechanism for the evolution of dual RNA motif recognition in Glo that may be applied to understanding the functional diversity of other RNA-binding proteins.

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Teaser

Tamayo et al. show that each of Drosophila Glorund's RNA-binding domains utilize two discrete modes of RNA recognition. Glorund's biological functions differ in the requirement for one or both recognition modes, suggesting a molecular mechanism for regulation of diverse RNA targets by Glorund and possibly other RNA-binding proteins.


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