@article{cd853a2f72f846a09aa7b913e5b22406,
title = "The Drosophila hnRNP F/H Homolog Glorund Uses Two Distinct RNA-Binding Modes to Diversify Target Recognition",
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.",
keywords = "Drosophila, Glorund, RNA-binding protein, development, hnRNP, hnRNP F, hnRNP H, nanos, post-transcriptional regulation, translational control, translational repressor",
author = "Tamayo, {Joel V.} and Takamasa Teramoto and Seema Chatterjee and Hall, {Traci M.Tanaka} and Gavis, {Elizabeth R.}",
note = "Funding Information: The authors would like to thank D. Snowflack and Y. Kalifa for initial studies, G. Laevsky for assistance with confocal microscopy, M. Niepielko for help with qPCR analysis, R. Petrovich of the NIEHS Protein Expression Core Facility for assistance with circular dichroism analysis, and L. Pedersen and the staff of the Southeast Regional Collaborative Access Team beamlines for assistance with X-ray data collection. We are grateful to G. Kissling for advice on statistical analyses, F. Hughson for helpful discussions, and E. Abbaszadeh and F. Hughson for critical comments on the manuscript. This research was supported in part by a National Science Foundation Graduate Research Fellowship awarded to J.V.T. (DGE 1148900), a Japan Society for the Promotion of Science Research Fellowship for Japanese Biomedical and Behavioral Researchers at NIH fellowship awarded to T.T., and grants from the National Institutes of Health to E.R.G. (R01 GM061107), and the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (T.M.T.H., 1ZIAES050165). The Advanced Photon Source used for this study is supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, under contract no. W-31-109-Eng-38. Publisher Copyright: {\textcopyright} 2017 The Author(s)",
year = "2017",
month = apr,
day = "4",
doi = "10.1016/j.celrep.2017.03.022",
language = "English (US)",
volume = "19",
pages = "150--161",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "1",
}