Nucleic acid-binding specificity of human FUS protein

• Published in: Nucleic acids research Vol. 43; no. 15; pp. 7535 - 7543
• Main Authors: Wang, Xueyin, Schwartz, Jacob C, Cech, Thomas R
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 03.09.2015
• Subjects: DNA - metabolism; DNA, Single-Stranded - metabolism; Humans; Nucleotide Motifs; Protein Binding; RNA; RNA - chemistry; RNA - metabolism; RNA-Binding Protein FUS - metabolism
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/gkv679

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.