title: Backbone-independent nucleic acid binding by splicing factor SUP-12 reveals key aspects of molecular recognition.
abstract: Cellular differentiation is frequently accompanied by alternative splicing, enabled by the expression of tissue-specific factors which bind to pre-mRNAs and regulate exon choice. During Caenorhabditis elegans development, muscle-specific expression of the splicing factor SUP-12, together with a member of the Fox-1 family of splicing proteins, generates a functionally distinct isoform of the fibroblast growth factor receptor EGL-15. Using a combination of NMR spectroscopy and isothermal titration calorimetry, we determined the mode of nucleic acid binding by the RNA recognition motif domain of SUP-12. The calculated structures provide the first atomic details of RNA and DNA binding by the family of proteins that include SUP-12, RBM24, RBM38/RNPC1, SEB-4 and XSeb4R. This information was further used to design strategic mutations to probe the interaction with ASD-1 and to quantitatively perturb splicing in vivo.
authors.affiliation: 1] Institut Européen de Chimie et Biologie, IECB, Univ. Bordeaux, 2 rue Robert Escarpit, F-33607 Pessac, France [2] Inserm, U869, ARNA Laboratory, 146 rue Léo Saignat, F-33076 Bordeaux, France.
authors.forename: Samir
authors.initials: S
authors.lastname: Amrane
authors.affiliation: 1] Institut Européen de Chimie et Biologie, IECB, Univ. Bordeaux, 2 rue Robert Escarpit, F-33607 Pessac, France [2] Inserm, U869, ARNA Laboratory, 146 rue Léo Saignat, F-33076 Bordeaux, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Rebora
authors.affiliation: 1] Institut Européen de Chimie et Biologie, IECB, Univ. Bordeaux, 2 rue Robert Escarpit, F-33607 Pessac, France [2] Inserm, U869, ARNA Laboratory, 146 rue Léo Saignat, F-33076 Bordeaux, France.
authors.forename: Ilyass
authors.initials: I
authors.lastname: Zniber
authors.affiliation: 1] Institut Européen de Chimie et Biologie, IECB, Univ. Bordeaux, 2 rue Robert Escarpit, F-33607 Pessac, France [2] Inserm, U869, ARNA Laboratory, 146 rue Léo Saignat, F-33076 Bordeaux, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Dupuy
authors.affiliation: 1] Institut Européen de Chimie et Biologie, IECB, Univ. Bordeaux, 2 rue Robert Escarpit, F-33607 Pessac, France [2] Inserm, U869, ARNA Laboratory, 146 rue Léo Saignat, F-33076 Bordeaux, France.
authors.forename: Cameron D
authors.initials: CD
authors.lastname: Mackereth
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002151:Calorimetry; D002454:Cell Differentiation; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins
chemical_list: C515945:Asd-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; C112493:EGL-15 protein, C elegans; C117552:FOX-1 protein, C elegans; D016601:RNA-Binding Proteins; D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins; C525043:Sup-12 protein, C elegans; D012313:RNA