Systematic Discovery of Endogenous Human Ribonucleoprotein Complexes

Cell Rep. 2019 Oct 29;29(5):1351-1368.e5. doi: 10.1016/j.celrep.2019.09.060.


RNA-binding proteins (RBPs) play essential roles in biology and are frequently associated with human disease. Although recent studies have systematically identified individual RNA-binding proteins, their higher-order assembly into ribonucleoprotein (RNP) complexes has not been systematically investigated. Here, we describe a proteomics method for systematic identification of RNP complexes in human cells. We identify 1,428 protein complexes that associate with RNA, indicating that more than 20% of known human protein complexes contain RNA. To explore the role of RNA in the assembly of each complex, we identify complexes that dissociate, change composition, or form stable protein-only complexes in the absence of RNA. We use our method to systematically identify cell-type-specific RNA-associated proteins in mouse embryonic stem cells and finally, distribute our resource, rna.MAP, in an easy-to-use online interface ( Our system thus provides a methodology for explorations across human tissues, disease states, and throughout all domains of life.

Keywords: DIF-FRAC; RBP; RNA-binding protein; RNP; biochemical fractionation; interactome; mass spectrometry; protein complexes; proteomics; ribonucleoprotein complex.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Fractionation
  • HEK293 Cells
  • Humans
  • Mice
  • Multiprotein Complexes / metabolism*
  • Nucleic Acid Conformation
  • Proteome / metabolism
  • RNA / chemistry
  • Replication Protein C / metabolism
  • Reproducibility of Results
  • Ribonucleoproteins / metabolism*


  • Multiprotein Complexes
  • Proteome
  • Ribonucleoproteins
  • RNA
  • Replication Protein C