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

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

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number2049
JournalNature communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Du, M., Yuan, L., Tan, X., Huang, D., Wang, X., Zheng, Z., Mao, X., Li, X., Yang, L., Huang, K., Zhang, F., Wang, Y., Luo, X., Huang, D., & Huang, K. (2017). The LPS-inducible lncRNA Mirt2 is a negative regulator of inflammation. Nature communications, 8(1), [2049]. https://doi.org/10.1038/s41467-017-02229-1