Characterizing ZC3H18, a Multi-domain Protein at the Interface of RNA Production and Destruction Decisions

Cell Rep. 2018 Jan 2;22(1):44-58. doi: 10.1016/j.celrep.2017.12.037.


Nuclear RNA metabolism is influenced by protein complexes connecting to both RNA-productive and -destructive pathways. The ZC3H18 protein binds the cap-binding complex (CBC), universally present on capped RNAs, while also associating with the nuclear exosome targeting (NEXT) complex, linking to RNA decay. To dissect ZC3H18 function, we conducted interaction screening and mutagenesis of the protein, which revealed a phosphorylation-dependent isoform. Surprisingly, the modified region of ZC3H18 associates with core histone proteins. Further examination of ZC3H18 function, by genome-wide analyses, demonstrated its impact on transcription of a subset of protein-coding genes. This activity requires the CBC-interacting domain of the protein, with some genes being also dependent on the NEXT- and/or histone-interacting domains. Our data shed light on the domain requirements of a protein positioned centrally in nuclear RNA metabolism, and they suggest that post-translational modification may modulate its function.

Keywords: CBC; NEXT; RNA decay; RNA exosome; ZC3H18; histones; transcription.

Publication types

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

MeSH terms

  • Cell Nucleus / chemistry
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism*
  • Genome-Wide Association Study
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Mutagenesis
  • Nuclear Cap-Binding Protein Complex / chemistry
  • Nuclear Cap-Binding Protein Complex / genetics
  • Nuclear Cap-Binding Protein Complex / metabolism*
  • Protein Domains
  • RNA / biosynthesis*
  • RNA / genetics
  • RNA Stability / physiology*
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*


  • Nuclear Cap-Binding Protein Complex
  • RNA-Binding Proteins
  • ZC3H18 protein, human
  • RNA