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Cell Rep. 2017 Apr 4;19(1):150-161. doi: 10.1016/j.celrep.2017.03.022.

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

Author information

1
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
2
Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
3
Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Electronic address: hall4@niehs.nih.gov.
4
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA. Electronic address: gavis@princeton.edu.

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

PMID:
28380354
PMCID:
PMC5392723
DOI:
10.1016/j.celrep.2017.03.022
[Indexed for MEDLINE]
Free PMC Article

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