title: Nucleic acid-binding specificity of human FUS protein.
abstract: FUS, a nuclear RNA-binding protein, plays multiple roles in RNA processing. Five specific FUS-binding RNA sequence/structure motifs have been proposed, but their affinities for FUS have not been directly compared. Here we find that human FUS binds all these sequences with Kd (app) values spanning a 10-fold range. Furthermore, some RNAs that do not contain any of these motifs bind FUS with similar affinity. FUS binds RNA in a length-dependent manner, consistent with a substantial non-specific component to binding. Finally, investigation of FUS binding to different nucleic acids shows that it binds single-stranded DNA with three-fold lower affinity than ssRNA of the same length and sequence, while binding to double-stranded nucleic acids is weaker. We conclude that FUS has quite general nucleic acid-binding activity, with the various proposed RNA motifs being neither necessary for FUS binding nor sufficient to explain its diverse binding partners.
authors.affiliation: Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, BioFrontiers Institute, University of Colorado, Boulder CO 80309, USA.
authors.forename: Xueyin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, BioFrontiers Institute, University of Colorado, Boulder CO 80309, USA.
authors.forename: Jacob C
authors.initials: JC
authors.lastname: Schwartz
authors.affiliation: Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, BioFrontiers Institute, University of Colorado, Boulder CO 80309, USA Thomas.Cech@colorado.edu.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Cech
mesh_terms: D004247:DNA / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000378:metabolism; D006801:Humans; D059372:Nucleotide Motifs; D011485:Protein Binding; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D034702:RNA-Binding Protein FUS / Q000378:metabolism*
chemical_list: D004277:DNA, Single-Stranded; C000599550:FUS protein, human; D034702:RNA-Binding Protein FUS; D012313:RNA; D004247:DNA