Nucleic acid-binding specificity of human FUS protein. Nucleic Acids Res

FUS, a nuclear RNA-binding protein, plays multi-ple 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 Kdapp values span-ning a 10-fold range. Furthermore, some RNAs that do not contain any of these motifs bind FUS with sim-ilar 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 mo-tifs being neither necessary for FUS binding nor suf-ficient to explain its diverse binding partners