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.
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Joel V
authors.initials: JV
authors.lastname: Tamayo
authors.affiliation: Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
authors.forename: Takamasa
authors.initials: T
authors.lastname: Teramoto
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Seema
authors.initials: S
authors.lastname: Chatterjee
authors.affiliation: 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.
authors.forename: Traci M Tanaka
authors.initials: TMT
authors.lastname: Hall
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA. Electronic address: gavis@princeton.edu.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Gavis
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D005260:Female; D034541:Heterogeneous-Nuclear Ribonucleoprotein Group F-H / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D059372:Nucleotide Motifs; D009865:Oocytes / Q000378:metabolism*; D010053:Ovary / Q000378:metabolism*; D014176:Protein Biosynthesis; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016211:Transforming Growth Factor alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; C509827:Glo protein, Drosophila; D034541:Heterogeneous-Nuclear Ribonucleoprotein Group F-H; D016601:RNA-Binding Proteins; D016211:Transforming Growth Factor alpha; C083730:grk protein, Drosophila; C070574:nos protein, Drosophila; D012313:RNA
keywords: Drosophila; Glorund; RNA-binding protein; development; hnRNP; hnRNP F; hnRNP H; nanos; post-transcriptional regulation; translational control; translational repressor