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

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

doi:10.1016/j.celrep.2019.03.006

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

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^*

^*Corresponding author af dette arbejde

13 Citationer (Scopus)

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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. 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.

Originalsprog	Engelsk
Tidsskrift	Cell Reports
Vol/bind	26
Udgave nummer	13
Sider (fra-til)	3511-3521.e4
Antal sider	16
ISSN	2211-1247
DOI	https://doi.org/10.1016/j.celrep.2019.03.006
Status	Udgivet - 26 mar. 2019

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10.1016/j.celrep.2019.03.006

GIGYF1/2-Driven Cooperation between ZNF598 and TTP in Posttranscriptional Regulation of Inflammatory SignalingForlagets udgivne version, 3,35 MB

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title = "GIGYF1/2-Driven Cooperation between ZNF598 and TTP in Posttranscriptional Regulation of Inflammatory Signaling",

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. 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.",

author = "Tollenaere, {Maxim A X} and Christopher Tiedje and Simon Rasmussen and Nielsen, {Julie C} and Vind, {Anna C} and Melanie Blasius and Batth, {Tanveer S} and Niels Mailand and Olsen, {Jesper V} and Matthias Gaestel and Simon Bekker-Jensen",

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AU - Tollenaere, Maxim A X

AU - Tiedje, Christopher

AU - Rasmussen, Simon

AU - Nielsen, Julie C

AU - Vind, Anna C

AU - Blasius, Melanie

AU - Batth, Tanveer S

AU - Mailand, Niels

AU - Olsen, Jesper V

AU - Gaestel, Matthias

AU - Bekker-Jensen, Simon

PY - 2019/3/26

Y1 - 2019/3/26

N2 - 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.

AB - 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.

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DO - 10.1016/j.celrep.2019.03.006

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JO - Cell Reports

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ER -

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

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