A long noncoding RNA, lincRNA‐Tnfaip3, acts as a coregulator of NF‐κB to modulate inflammatory gene transcription in mouse macrophages

Abstract

ABSTRACT Long intergenic noncoding RNAs (lincRNAs) are long noncoding transcripts (>200 nt) from the intergenic regions of annotated protein‐coding genes. We report here that the lincRNA gene lincRNA‐Tnfaip3 , located at mouse chromosome 10 proximal to the tumor necrosis factor α‐induced protein 3 ( Tnfaip3 ) gene, is an early‐primary response gene controlled by nuclear factor‐κB (NF‐κB) signaling in murine macrophages. Functionally, lincRNA‐ Tnfaip3 appears to mediate both the activation and repression of distinct classes of inflammatory genes in macrophages. Specifically, induction of lincRNA‐Tnfaip3 is required for the transactivation of NF‐κB‐regulated inflammatory genes in response to bacterial LPSs stimulation. LincRNA‐Tnfaip3 physically interacts with the high‐mobility group box 1 (Hmgb1), assembling a NF‐κB/Hmgb1/lincRNA‐Tnfaip3 complex in macrophages after LPS stimulation. This resultant NF‐κB/Hmgb1/lincRNA‐Tnfaip3 complex can modulate Hmgb1‐associated histone modifications and, ultimately, transactivation of inflammatory genes in mouse macrophages in response to microbial challenge. Therefore, our data indicate a new regulatory role of NF‐κB‐induced lincRNA‐Tnfaip3 to act as a coactivator of NF‐κB for the transcription of inflammatory genes in innate immune cells through modulation of epigenetic chromatin remodeling.—Ma, S., Ming, Z., Gong, A.‐Y., Wang, Y., Chen, X., Hu, G., Zhou, R., Shibata, A., Swanson, P. C., Chen, X.‐M. A long noncoding RNA, LincRNA‐Tnfaip3, acts as a coregulator of NF‐κB to modulate inflammatory gene transcription in mouse macrophages. FASEB J. 31, 1215–1225 (2017). www.fasebj.org