TY - JOUR
T1 - Characterizing ZC3H18, a Multi-domain Protein at the Interface of RNA Production and Destruction Decisions
AU - Winczura, Kinga
AU - Schmid, Manfred
AU - Iasillo, Claudia
AU - Molloy, Kelly R
AU - Harder, Lea Mørch
AU - Andersen, Jens S
AU - LaCava, John
AU - Jensen, Torben Heick
N1 - Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
PY - 2018/1/2
Y1 - 2018/1/2
N2 - 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. The ZC3H18 protein is involved in RNA decay mediated by the CBC-NEXT complex. Winczura et al. identify a phosphorylation-dependent interaction of ZC3H18 with histones, and they find separate CBCA-, NEXT-, and histone-binding domains. They suggest a role for ZC3H18 in mRNA biogenesis, which for some genes is independent of its role in RNA decay.
AB - 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. The ZC3H18 protein is involved in RNA decay mediated by the CBC-NEXT complex. Winczura et al. identify a phosphorylation-dependent interaction of ZC3H18 with histones, and they find separate CBCA-, NEXT-, and histone-binding domains. They suggest a role for ZC3H18 in mRNA biogenesis, which for some genes is independent of its role in RNA decay.
KW - Journal Article
UR - http://www.scopus.com/inward/record.url?scp=85041644837&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2017.12.037
DO - 10.1016/j.celrep.2017.12.037
M3 - Journal article
C2 - 29298432
SN - 2211-1247
VL - 22
SP - 44
EP - 58
JO - Cell Reports
JF - Cell Reports
IS - 1
ER -