FIGURE 5.

LncRNA regulation and feedback loops in IFN-I production and ISG expression. PAMPs or foreign nucleic acid are sensed by TLRs and RIG-I, respectively. The TLR pathway activates IRF6 and NF-κB through TRAF6, whereas RIG-I activates IRF3/7 directly, leading to their nuclear translocation and IFN-I expression. IFN-I can then stimulate IFNAR in either autocrine or paracrine manners to trigger a STAT1/2/3-mediated pathway, promoting ISG expression. LncRNAs regulate one or more elements in the IFN-I production cascade, including activation of TRAF6 and RIG-I by NEAT1, activation of NF-κB by MALAT1 and PACER, or inhibition of NF-κB by THRIL and Lethe. EGOT forms a negative feedback loop, itself is induced by TLR and RIG-1 pathways but also regulates IFN-1 induced responses by inhibiting the expression of ISG and other anti-viral lncRNAs such as NeST and BISPR.