Emerging Roles of lncRNAs Regulating RNA-Mediated Type-I Interferon Signaling Pathway

Abstract

The type-I interferon (IFN-I) signaling pathway plays pivot roles in defending against pathogen invasion. Exogenous ssRNA and dsRNA could be immunogenic. RNA-mediated IFN signaling is extensively studied in the field. The incorrect functioning of this pathway leads to either autoimmune diseases or suffering from microorganism invasion. From the discrimination of “self” and “non-self” molecules by receptors to the fine-tune modulations in downstream cascades, all steps are under the surveillance featured by complex feedbacks and regulators. Studies in recent years highlighted the emerging roles of long noncoding RNAs (lncRNAs) as a reservoir for signaling regulation. LncRNAs bind to targets through the structure and sequence, and thus the mechanisms of action can be complex and specific. Here, we summarized lncRNAs modulating the RNA-activated IFN-I signaling pathway according to the event order during the signaling. We hope this review help understand how lncRNAs are participating in the regulation of IFN-I signaling.

Immunomodulatory LncRNA on antisense strand of ICAM-1 augments SARS-CoV-2 infection-associated airway mucoinflammatory phenotype

“…In contrast, the upstream mediator DDX58 mRNA expression was significantly induced in cells with suppressed LASI lncRNA levels and IFIH1 mRNA trending toward a higher expression; this noted incongruity between type 1 IFN and its mediators needs more careful analysis, as it could potentially involve the RIG-1-like receptors engaged by siRNAs used for silencing LASI expression in our experimental set-up (Song and Rossi, 2017;van der Veen et al, 2018). Recent studies have also highlighted the differential role of DDX58 and IFIH1 in innate immune responses to CoV-2 infection and the role of the cellular lncRNAs therein (Brisse and Ly, 2019;Ji et al, 2022;Yang et al, 2021). However, the changes in IRF3 and DDX58 expression can also be a cause or consequence of lower infectivity in our experimental set-up as well as in the nasal samples analyzed.…”

Single-cell analysis of signalling and transcriptional responses to type I interferons

“…Several lncRNAs are associated with the antiviral response and regulate the activity of pattern recognition receptors and signalling pathways leading to cytokine production, including the type I IFN signalling pathway. 43,49 These included NRIR (Negative Regulator of the Interferon Response) 50 , previously implicated in driving a type I IFN signature in monocytes in human autoimmune disease and viral infection. [51][52][53] Indeed, NRIR was differentially expressed in our dataset (Figure S12g).…”

Regulation of IFNβ expression: focusing on the role of its promoter and transcription regulators

“…At present, microRNAs (miRNAs) and lncRNAs are main non-coding RNAs that regulate gene expression ( Muntyanu et al, 2021 ; Chen et al, 2022 ; Ji et al, 2022 ). Lnc-MxA is a non-coding RNA that directly interacts with the IFNβ promoter, thereby forming an RNA–DNA triplex with the IFNβ promoter.…”