Nucleic acid-binding specificity of human FUS protein

Nucleic Acids Res. 2015 Sep 3;43(15):7535-43. doi: 10.1093/nar/gkv679. Epub 2015 Jul 6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / metabolism
  • DNA, Single-Stranded / metabolism
  • Humans
  • Nucleotide Motifs
  • Protein Binding
  • RNA / chemistry
  • RNA / metabolism*
  • RNA-Binding Protein FUS / metabolism*


  • DNA, Single-Stranded
  • FUS protein, human
  • RNA-Binding Protein FUS
  • RNA
  • DNA