Comprehensive Identification of RNA-Binding Domains in Human Cells

Mol Cell. 2016 Aug 18;63(4):696-710. doi: 10.1016/j.molcel.2016.06.029. Epub 2016 Jul 21.


Mammalian cells harbor more than a thousand RNA-binding proteins (RBPs), with half of these employing unknown modes of RNA binding. We developed RBDmap to determine the RNA-binding sites of native RBPs on a proteome-wide scale. We identified 1,174 binding sites within 529 HeLa cell RBPs, discovering numerous RNA-binding domains (RBDs). Catalytic centers or protein-protein interaction domains are in close relationship with RNA-binding sites, invoking possible effector roles of RNA in the control of protein function. Nearly half of the RNA-binding sites map to intrinsically disordered regions, uncovering unstructured domains as prevalent partners in protein-RNA interactions. RNA-binding sites represent hot spots for defined posttranslational modifications such as lysine acetylation and tyrosine phosphorylation, suggesting metabolic and signal-dependent regulation of RBP function. RBDs display a high degree of evolutionary conservation and incidence of Mendelian mutations, suggestive of important functional roles. RBDmap thus yields profound insights into native protein-RNA interactions in living cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Computational Biology
  • Databases, Protein
  • Evolution, Molecular
  • HeLa Cells
  • Humans
  • Methylation
  • Models, Molecular
  • Mutation
  • Nucleic Acid Conformation
  • Phosphorylation
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Processing, Post-Translational
  • Proteomics / methods*
  • RNA / chemistry
  • RNA / genetics
  • RNA / metabolism*
  • RNA-Binding Motifs*
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Structure-Activity Relationship


  • RNA-Binding Proteins
  • RNA