The Clock-Controlled lncRNA-AK028245 Participates in the Immune Response via Immune Response Factors OTUD7B and A20.

Abstract

Emerging evidence has demonstrated that long noncoding RNAs (lncRNAs) play critical roles in the epigenetic and transcriptional regulation of mammalian circadian systems. Circadian rhythmicity regulates many aspects of our immune system, and perturbation of the circadian clock can augment the inflammatory response. However, knowledge of the precise functions of lncRNAs in the regulation of immune functions within the circadian system is relatively limited. In this study, differentially expressed lncRNAs induced by Clock knockdown were screened via mRNA/lncRNA microarray and bioinformatic prediction analysis. We identified a Clock-regulated lncRNA, AK028245, which was correlated with the activation of the immune response. The expression levels of AK028245 were decreased in the spleen of immunosuppressed mice and elevated in immune-activated mice treated with lipopolysaccharide (LPS). Further, Clock knockdown decreased the expression of OTUD7B and A20, 2 early immune response factors acting on the NF-κB signaling pathway. Interestingly, inhibition of AK028245 increased their expression, mitigating the effects of Clock knockdown. In addition, inhibition of AK028245 downregulated the expression of tumor necrosis factor-α and interleukin-6 in the late stages of LPS stimulation and the expression of interferon-γ and Cxcl12 in the peak stages. We conclude that this newly identified lncRNA plays a role in the crosstalk between Clock and immune response regulators, likely resulting in a proinflammatory response targeting OTUD7B and A20. The lncRNA AK028245 has revealed a new mechanism of the immune response and provided new targets for the treatment of immune disorders.

• Authors: Fang Qi, Zhou Jiang, Wang Hou, Bo Peng, Shuting Cheng, Xiaolong Zhang, Zhihan Luo, Zeyong Dai, Yumeng Wang, Yanyou Liu, Yuhui Wang, Zhengrong Wang
• Journal: Journal of biological rhythms (J Biol Rhythms) Vol. 35 Issue 6 Pg. 542-554 (12 2020) ISSN: 1552-4531 [Electronic] United States
• PMID: 32748687 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lipopolysaccharides
• RNA, Long Noncoding
• RNA, Messenger
• long noncoding RNA AK028326, mouse
• Endopeptidases
• Otud7b protein, mouse
• Tumor Necrosis Factor alpha-Induced Protein 3
• Tnfaip3 protein, mouse

Topics

• Animals
• Circadian Clocks (genetics)
• Circadian Rhythm (genetics)
• Endopeptidases (immunology)
• Immunity (genetics)
• Lipopolysaccharides (immunology)
• Male
• Mice
• Mice, Inbred ICR
• RNA, Long Noncoding (genetics)
• RNA, Messenger
• Tumor Necrosis Factor alpha-Induced Protein 3 (immunology)