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

TitleThe Drosophila hnRNP F/H Homolog Glorund Uses Two Distinct RNA-Binding Modes to Diversify Target Recognition.
Publication TypeJournal Article
Year of Publication2017
AuthorsTamayo, JV, Teramoto, T, Chatterjee, S, Hall, TMTanaka, Gavis, ER
JournalCell Rep
Volume19
Issue1
Pagination150-161
Date Published2017 Apr 04
ISSN2211-1247
Abstract

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.

DOI10.1016/j.celrep.2017.03.022
Alternate JournalCell Rep
PubMed ID28380354
PubMed Central IDPMC5392723
Grant ListR01 GM061107 / GM / NIGMS NIH HHS / United States
ZIA ES050165-19 / / Intramural NIH HHS / United States