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

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  • Kinga Winczura
  • ,
  • Manfred Schmid
  • Claudia Iasillo
  • ,
  • Kelly R Molloy, Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
  • ,
  • Lea Mørch Harder, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, 5230 Odense M (Denmark).
  • ,
  • Jens S Andersen, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, 5230 Odense M (Denmark).
  • ,
  • John LaCava, Laboratory of Cellular and Structural Biology, Rockefeller University, 1230 York Avenue, New York, NY 10065, USA; Institute for Systems Genetics, Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA.
  • ,
  • Torben Heick Jensen

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.

Original languageEnglish
JournalCell Reports
Volume22
Issue1
Pages (from-to)44-58
Number of pages15
ISSN2211-1247
DOIs
Publication statusPublished - 2 Jan 2018

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  • Journal Article

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