Affinity proteomic dissection of the human nuclear cap-binding complex interactome

Nucleic Acids Res. 2020 Oct 9;48(18):10456-10469. doi: 10.1093/nar/gkaa743.


A 5',7-methylguanosine cap is a quintessential feature of RNA polymerase II-transcribed RNAs, and a textbook aspect of co-transcriptional RNA processing. The cap is bound by the cap-binding complex (CBC), canonically consisting of nuclear cap-binding proteins 1 and 2 (NCBP1/2). Interest in the CBC has recently renewed due to its participation in RNA-fate decisions via interactions with RNA productive factors as well as with adapters of the degradative RNA exosome. A novel cap-binding protein, NCBP3, was recently proposed to form an alternative CBC together with NCBP1, and to interact with the canonical CBC along with the protein SRRT. The theme of post-transcriptional RNA fate, and how it relates to co-transcriptional ribonucleoprotein assembly, is abundant with complicated, ambiguous, and likely incomplete models. In an effort to clarify the compositions of NCBP1-, 2- and 3-related macromolecular assemblies, we have applied an affinity capture-based interactome screen where the experimental design and data processing have been modified to quantitatively identify interactome differences between targets under a range of experimental conditions. This study generated a comprehensive view of NCBP-protein interactions in the ribonucleoprotein context and demonstrates the potential of our approach to benefit the interpretation of complex biological pathways.

Publication types

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

MeSH terms

  • Cytoplasm / immunology
  • Exosome Multienzyme Ribonuclease Complex / genetics
  • Humans
  • Nuclear Cap-Binding Protein Complex / genetics*
  • Nuclear Proteins / genetics*
  • Proteome / genetics*
  • Proteomics / methods
  • RNA Cap-Binding Proteins / genetics*
  • RNA Caps / genetics
  • RNA Polymerase II / genetics


  • Nuclear Cap-Binding Protein Complex
  • Nuclear Proteins
  • Proteome
  • RNA Cap-Binding Proteins
  • RNA Caps
  • SRRT protein, human
  • RNA Polymerase II
  • Exosome Multienzyme Ribonuclease Complex