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The LPS-inducible lncRNA Mirt2 is a negative regulator of inflammation

by Mao, Xiaoxiang , Yang, Liu , Huang, Kun , Wang, Yan , Zheng, Zhe , Du, Meng , Yuan, Lin , Tan, Xin , Huang, Dandan , Li, Xiangrao , Luo, Xi , Wang, Xiaojing , Huang, Dan , Zhang, Fengxiao , Huang, Kai

in 631/250/256/2516 / 631/337/384/2568 / Aberration / Cell activation / Cytokines / Endotoxemia / Gene transfer / Humanities and Social Sciences / Immune response / Immune system / Inflammation / Innate immunity / Lipopolysaccharides / Macrophages / MAP kinase / multidisciplinary / Negative feedback / NF-κB protein / Non-coding RNA / Pattern recognition / Pattern recognition receptors / Proteins / Receptor mechanisms / Receptors / Ribonucleic acid / RNA / Rodents / Science / Science (multidisciplinary) / Signal transduction / Signaling / TLR4 protein / Toll-like receptors / TRAF6 protein / Ubiquitin / Ubiquitin-protein ligase / Ubiquitination

2017

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2017

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2017

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Journal Article

The LPS-inducible lncRNA Mirt2 is a negative regulator of inflammation

Mao, Xiaoxiang,

Yang, Liu,

Huang, Kun,

Wang, Yan,

Zheng, Zhe,

Du, Meng,

Yuan, Lin,

Tan, Xin,

Huang, Dandan,

Li, Xiangrao,

Luo, Xi,

Wang, Xiaojing,

Huang, Dan,

Zhang, Fengxiao,

Huang, Kai

2017

Overview

Toll-like receptors (TLRs) are a family of pattern recognition receptors (PRR) with a crucial function in innate immune responses. Activation of TLR4 signaling at the plasma membrane by lipopolysaccharide (LPS) stimulates proinflammatory signaling pathways dependent on the E3 ubiquitin ligase TRAF6. Here we show the LPS-induced long non-coding RNA (lncRNA) Mirt2 functions as a checkpoint to prevent aberrant activation of inflammation, and is a potential regulator of macrophage polarization. Mirt2 associates with, and attenuates Lys63 (K63)-linked ubiquitination of, TRAF6, thus inhibiting activation of NF-κB and MAPK pathways and limiting production of proinflammatory cytokines. Adenovirus mediated gene transfer of Mirt2 protects mice from endotoxemia induced fatality and multi-organ dysfunction. These findings identify lncRNA Mirt2 as a negative feedback regulator of excessive inflammation. Excessive inflammation can be tissue destructive and contributes to auotinflammatory diseases and sepsis pathology. Here the authors show that the lncRNA Mirt2 is an endogenous negative feedback regulator of LPS-induced inflammation by limiting ubiquitination of TRAF6 and NF-κB activation.

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Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio

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