Format

Send to

Choose Destination
Cell Rep. 2019 Mar 26;26(13):3511-3521.e4. doi: 10.1016/j.celrep.2019.03.006.

GIGYF1/2-Driven Cooperation between ZNF598 and TTP in Posttranscriptional Regulation of Inflammatory Signaling.

Author information

1
Department of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
2
Department of Plant and Environmental Sciences, Copenhagen Plant Science Centre, University of Copenhagen, 1871 Frederiksberg, Denmark.
3
Mass Spectrometry for Quantitative Proteomics, Proteomics Program, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
4
Ubiquitin Signaling Group, Protein Signaling Program, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
5
Institute of Cell Biochemistry, Hannover Medical School (MHH), 30625 Hannover, Germany.
6
Department of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark. Electronic address: sbj@sund.ku.dk.

Abstract

Inflammatory signaling is restricted through degradation and the translational repression of cytokine mRNAs. A key factor in this regulation is tristetraprolin (TTP), an RNA-binding protein (RBP) that recruits RNA-destabilizing factors and the translation inhibitory complex 4EHP-GIGYF1/2 to AU-rich element (ARE)-containing mRNAs. Here, we show that the RBP ZNF598 contributes to the same regulatory module in a TTP-like manner. Similar to TTP, ZNF598 harbors three proline-rich motifs that bind the GYF domain of GIGYF1. RNA sequencing experiments showed that ZNF598 is required for the regulation of known TTP targets, including IL-8 and CSF2 mRNA. Furthermore, we demonstrate that ZNF598 binds to IL-8 mRNA, but not TNF mRNA. Collectively, our findings highlight that ZNF598 functions as an RBP that buffers the level of a range of mRNAs. We propose that ZNF598 is a TTP-like factor that can contribute to the regulation of the inflammatory potential of cytokine-producing cells.

PMID:
30917308
DOI:
10.1016/j.celrep.2019.03.006
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center