RDUR, a lncRNA, Promotes Innate Antiviral Responses and Provides Feedback Control of NF-κB Activation

Abstract

Influenza A virus (IAV), a highly infectious respiratory pathogen, remains a major threat to global public health. Numerous long non-coding RNAs (lncRNAs) have been shown to be implicated in various cellular processes. Here, we identified a new lncRNA termed RIG-I-dependent IAV-upregulated noncoding RNA (RDUR), which was induced by infections with IAV and several other viruses. Both in vitro and in vivo studies revealed that robust expression of host RDUR induced by IAV was dependent on the RIG-I/NF-κB pathway. Overexpression of RDUR suppressed IAV replication and downregulation of RDUR promoted the virus replication. Deficiency of mouse RDUR increased virus production in lungs, body weight loss, acute organ damage and consequently reduced survival rates of mice, in response to IAV infection. RDUR impaired the viral replication by upregulating the expression of several vital antiviral molecules including interferons (IFNs) and interferon-stimulated genes (ISGs). Further study showed that RDUR interacted with ILF2 and ILF3 that were required for the efficient expression of some ISGs such as IFITM3 and MX1. On the other hand, we found that while NF-κB positively regulated the expression of RDUR, increased expression of RDUR, in turn, inactivated NF-κB through a negative feedback mechanism to suppress excessive inflammatory response to viral infection. Together, the results demonstrate that RDUR is an important lncRNA acting as a critical regulator of innate immunity against the viral infection.

Influenza A Virus-Induced circRNA circMerTK Negatively Regulates Innate Antiviral Responses

“…To determine whether other pattern recognition receptors (PRRs) and signaling molecules are involved in the regulation of circMerTK expression, we employed several cell lines stably expressing short hairpin RNAs (shRNAs) specifically targeting PRRs or signaling molecules, as previously described ( 24 – 26 ). We observed that knockdown of interferon regulatory factor (IRF) 3, IRF7, and mitochondrial antiviral-signaling protein (MAVS) significantly reduced circMerTK levels following IAV infection, but knockdown of antimelanoma differentiation-associated gene 5 (MDA5) had no significant impact on circMerTK expression ( Fig.…”

Transcriptome-wide 5-methylcytosine modification profiling of long non-coding RNAs in A549 cells infected with H1N1 influenza A virus

“…Several IAV-upregulated lncRNAs have been found to inhibit IAV replication. For example, lnc-ISG20 [ 25 ] and ISR [ 29 ] function as interferon-stimulated genes (ISGs), and LncRNA-155 [ 26 ], NEAT1 [ 39 ], SAAL [ 40 ], RDUR [ 41 ], AVAN [ 42 ] and IVRPIE [ 43 ] can suppress IAV replication by promoting innate immune responses to viral infection. However, it remains unknown how the expression levels of these lncRNAs are regulated and whether RNA modifications play roles in the lncRNA regulation in response to the virus infection.…”

Differential expression profile and in-silico functional analysis of long noncoding RNA and mRNA in duck embryo fibroblasts infected with duck plague virus

“…For example, RIG-I-dependent IAV upregulated noncoding RNA (RDUR), induced by Influenza A virus (IAV) infection, can positively regulate the signal transduction of type I interferon (IFN-1) by affecting IRF3 and further upregulates the expression of several vital antiviral molecules. It is concluded that RDUR is a critical regulator of innate immunity against viral infection [ 27 ]. And lncRNA-GM can bind to glutathione S-transferase M1 (GSTM1), block the interaction between GSTM1 and TANK binding kinase 1 (TBK1), and reduce GSTM1-mediated glutathione.…”