GIGYF1/2-Driven Cooperation between ZNF598 and TTP in Posttranscriptional Regulation of Inflammatory Signaling
Summary: 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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-03-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719303134 |
| _version_ | 1818839332730961920 |
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| author | Maxim A.X. Tollenaere Christopher Tiedje Simon Rasmussen Julie C. Nielsen Anna C. Vind Melanie Blasius Tanveer S. Batth Niels Mailand Jesper V. Olsen Matthias Gaestel Simon Bekker-Jensen |
| author_facet | Maxim A.X. Tollenaere Christopher Tiedje Simon Rasmussen Julie C. Nielsen Anna C. Vind Melanie Blasius Tanveer S. Batth Niels Mailand Jesper V. Olsen Matthias Gaestel Simon Bekker-Jensen |
| author_sort | Maxim A.X. Tollenaere |
| collection | DOAJ |
| description | Summary: 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. : Tollenaere et al. highlight a structural and functional resemblance between the ribosome-associated ubiquitin ligase ZNF598 and TTP, the negative regulator of inflammation-associated mRNA stability. Like TTP, ZNF598 contains proline stretches that are bound by GYF domain-containing proteins, binds cytokine mRNAs, and represses inflammatory signaling in resting cells. |
| first_indexed | 2024-12-19T03:52:37Z |
| format | Article |
| id | doaj.art-5588f8057b1148499dbf19a354bfd526 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-19T03:52:37Z |
| publishDate | 2019-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-5588f8057b1148499dbf19a354bfd5262022-12-21T20:36:54ZengElsevierCell Reports2211-12472019-03-01261335113521.e4GIGYF1/2-Driven Cooperation between ZNF598 and TTP in Posttranscriptional Regulation of Inflammatory SignalingMaxim A.X. Tollenaere0Christopher Tiedje1Simon Rasmussen2Julie C. Nielsen3Anna C. Vind4Melanie Blasius5Tanveer S. Batth6Niels Mailand7Jesper V. Olsen8Matthias Gaestel9Simon Bekker-Jensen10Department of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, DenmarkDepartment of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, DenmarkDepartment of Plant and Environmental Sciences, Copenhagen Plant Science Centre, University of Copenhagen, 1871 Frederiksberg, DenmarkDepartment of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, DenmarkDepartment of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, DenmarkDepartment of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, DenmarkMass 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, DenmarkUbiquitin 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, DenmarkMass 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, DenmarkInstitute of Cell Biochemistry, Hannover Medical School (MHH), 30625 Hannover, GermanyDepartment of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark; Corresponding authorSummary: 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. : Tollenaere et al. highlight a structural and functional resemblance between the ribosome-associated ubiquitin ligase ZNF598 and TTP, the negative regulator of inflammation-associated mRNA stability. Like TTP, ZNF598 contains proline stretches that are bound by GYF domain-containing proteins, binds cytokine mRNAs, and represses inflammatory signaling in resting cells.http://www.sciencedirect.com/science/article/pii/S2211124719303134 |
| spellingShingle | Maxim A.X. Tollenaere Christopher Tiedje Simon Rasmussen Julie C. Nielsen Anna C. Vind Melanie Blasius Tanveer S. Batth Niels Mailand Jesper V. Olsen Matthias Gaestel Simon Bekker-Jensen GIGYF1/2-Driven Cooperation between ZNF598 and TTP in Posttranscriptional Regulation of Inflammatory Signaling Cell Reports |
| title | GIGYF1/2-Driven Cooperation between ZNF598 and TTP in Posttranscriptional Regulation of Inflammatory Signaling |
| title_full | GIGYF1/2-Driven Cooperation between ZNF598 and TTP in Posttranscriptional Regulation of Inflammatory Signaling |
| title_fullStr | GIGYF1/2-Driven Cooperation between ZNF598 and TTP in Posttranscriptional Regulation of Inflammatory Signaling |
| title_full_unstemmed | GIGYF1/2-Driven Cooperation between ZNF598 and TTP in Posttranscriptional Regulation of Inflammatory Signaling |
| title_short | GIGYF1/2-Driven Cooperation between ZNF598 and TTP in Posttranscriptional Regulation of Inflammatory Signaling |
| title_sort | gigyf1 2 driven cooperation between znf598 and ttp in posttranscriptional regulation of inflammatory signaling |
| url | http://www.sciencedirect.com/science/article/pii/S2211124719303134 |
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