Abstract
Non-coding RNAs represent a class of important regulators in immune response. Previously, LINC02605 was identified as a candidate regulator in innate immune response by lncRNA microarray assays. In this study, we systematically analyzed the functions and the acting mechanisms of LINC02605 in antiviral innate immune response. LINC02605 was up-regulated by RNA virus, DNA virus, and type I IFNs in NF-κB and Jak-stat dependent manner. Overexpression of LINC02605 promotes RNA virus-induced type I interferon production and inhibited viral replication. Consistently, knockdown of LINC02605 resulted in reduced antiviral immune response and increased viral replication. Mechanistically, LINC02605 released the inhibition of hsa-miR-107 on the expression of phosphatase and tensin homolog (PTEN). By microRNA mimics and inhibitors, hsa-miR-107 was demonstrated to not only inhibit PTEN’s expression but also negatively regulate the antiviral immune response. Knockdown of LINC02605 led to the reduction of PTEN expression both in mRNA and protein levels. Overexpression of LINC02605 had an opposite impact. Moreover, LINC02605 attenuated the serine 97 phosphorylation level of interferon regulatory factor 3 (IRF3) by promoting PTEN expression. Nucleoplasmic fragmentation assay showed that knocking down LINC02605 inhibited the nuclear translocation of IRF3, rendering the host cells more susceptible to viral invasion, while overexpression showed opposite effects. Therefore, LINC02605 is an induced lncRNA by viral infection and plays a positive feedback in antiviral immune response through modulating the nuclear translocation of IRF3.
Highlights
Upon viral infection, viral nucleic acids are initially recognized by a diverse set of pattern recognition receptors (PRRs) [1]
In order to screen potential novel regulators in RNA virus-induced signaling pathway, by microarray analysis, LINC02605 is identified as a candidate regulator that may be involved in modulating antiviral innate immune response [21]
LncRNAs are non-coding RNAs with lengths greater than 200 nucleotides, which are involved in the regulation of many biological functions, including cell cycle regulation, cell differentiation, and immune response [25]
Summary
Viral nucleic acids are initially recognized by a diverse set of pattern recognition receptors (PRRs) [1]. After binding viral nucleic acids, the PRRs activate downstream signaling pathways by adaptor proteins such as MAVS or STING, trigger the signaling cascades, eventually lead to the production of proinflammatory cytokines and type I interferons [7]. The remaining transcription products are named as non-coding RNAs (ncRNAs). Long non-coding RNAs (lncRNAs) are a class of ncRNAs which are over 200 nucleotides in length with no protein-coding potential. LncRNAs can perform their functions by interacting with protein, RNA, DNA and acting as a decoy, scaffold, guide, sponge etc., to regulate gene transcription, protein translation and functions. It is possible that in some instances, lncRNAs function with their peptide-encoding capacity, concurrently with or without their noncoding RNA functions
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
