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Review
. 2021 Jan 19;10(1):66.
doi: 10.3390/biology10010066.

Role of Tristetraprolin in the Resolution of Inflammation

Peter Rappl  1 , Bernhard Brüne  1   2   3   4 , Tobias Schmid  1
Affiliations
Review

Role of Tristetraprolin in the Resolution of Inflammation

Peter Rappl et al. Biology (Basel). .

Abstract

Inflammation is a crucial part of immune responses towards invading pathogens or tissue damage. While inflammatory reactions are aimed at removing the triggering stimulus, it is important that these processes are terminated in a coordinate manner to prevent excessive tissue damage due to the highly reactive inflammatory environment. Initiation of inflammatory responses was proposed to be regulated predominantly at a transcriptional level, whereas post-transcriptional modes of regulation appear to be crucial for resolution of inflammation. The RNA-binding protein tristetraprolin (TTP) interacts with AU-rich elements in the 3' untranslated region of mRNAs, recruits deadenylase complexes and thereby facilitates degradation of its targets. As TTP regulates the mRNA stability of numerous inflammatory mediators, it was put forward as a crucial post-transcriptional regulator of inflammation. Here, we summarize the current understanding of the function of TTP with a specific focus on its role in adding to resolution of inflammation.

Keywords: AU-rich element; RNA-binding protein; mRNA stability; post-transcriptional regulation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Distinct phases of an acute, transient inflammatory process and the respective macrophage subtypes (MO: monocyte; Mϕ: macrophage).
Figure 2
Figure 2
Tristetraprolin (TTP) protein structure, activity regulation, and function. (a) p38-MAPK activates MK2, which phosphorylates TTP at serines 52 and 178 (mouse), which allows for binding of 14-3-3 and inactivation of TTP. DUSP 1 inhibits p38-MAPK. (NES: nuclear export signal; NOT1 BD: NOT1 binding domain) (b) TTP interacts with adenosine and uridine (AU)-rich elements (AREs) in the 3′ untranslated region of target mRNAs and recruits the CCR4-NOT deadenylation complex, facilitating rapid degradation of the target mRNA. (ORF: open reading frame).
Figure 3
Figure 3
TTP activity (violet) and targets (green: feedback regulators; red: inflammatory; blue: anti-inflammatory) in macrophages during the early phases of inflammation.
See this image and copyright information in PMC

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