In silico analysis of altered expression of long non-coding RNA in SARS-CoV-2 infected cells and their possible regulation by STAT1, STAT3 and interferon regulatory factors

Abstract

Altered expression of long noncoding RNA (lncRNA), longer than 200 nucleotides without potential for coding protein, has been observed in diverse human diseases including viral diseases. It is largely unknown whether lncRNA would deregulate in SARS-CoV-2 infection, causing ongoing pandemic COVID-19. To identify, if lncRNA was deregulated in SARS-CoV-2 infected cells, we analyzed in silico the data in GSE147507. It was revealed that expression of 20 lncRNA like MALAT1, NEAT1 was increased and 4 lncRNA like PART1, TP53TG1 was decreased in at least two independent cell lines infected with SARS-CoV-2. Expression of NEAT1 was also increased in lungs tissue of COVID-19 patients. The deregulated lncRNA could interact with more than 2800 genes/proteins and 422 microRNAs as revealed from the database that catalogs experimentally determined interactions. Analysis with the interacting gene/protein partners of deregulated lncRNAs revealed that these genes/proteins were associated with many pathways related to viral infection, inflammation and immune functions. To find out whether these lncRNAs could be regulated by STATs and interferon regulatory factors (IRFs), we used ChIPBase v2.0 that catalogs experimentally determined binding from ChIP-seq data. It was revealed that any one of the transcription factors IRF1, IRF4, STAT1, STAT3 and STAT5A had experimentally determined binding at regions within -5kb to +1kb of the deregulated lncRNAs in at least 2 independent cell lines/conditions. Our analysis revealed that several lncRNAs could be regulated by IRF1, IRF4 STAT1 and STAT3 in response to SARS-CoV-2 infection and lncRNAs might be involved in antiviral response. However, these in silico observations are necessary to be validated experimentally.

Long noncoding RNAs in respiratory viruses: A review

“…Reduced levels of Type I/III interferon response have been observed in animal models, different tissues from coronavirus disease 2019 (Covid‐19) patients and infected cells with SARS‐CoV‐2. 68 In contrast, increased levels of Type I IFN genes in Covid‐19 patients and SARS‐CoV‐2 infected organoid have been observed. Differences in results may be related to use of different cell types, mixture of cell types or sampling at different times of the disease.…”

“… 48 , 66 , 67 Increased expression of EGOT is observed in IAV infection and it may promote viral replication by controlling the levels of the transcriptional coactivator T‐Box protein 1 (TBXL1) and ISGs leading to blocking the IFN antiviral response. 48 , 53 , 68 Inhibition of EGOT leads to increased levels of several ISGs and to decreased viral replication.…”

Genome interaction of the virus and the host genes and non-coding RNAs in SARS-CoV-2 infection

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Noncoding RNA therapeutics — challenges and potential solutions

“…Moreover, endogenous miRNAs may target proteins required for viral entry such as the ACE2 receptor (miR-200c) 337 or the neural-entry cofactor neuropilin-1 (miR-24) 338 . Last, SARS-CoV-2 strongly influences the noncoding transcriptome of infected cells, affecting the expression of miRNA 339 as well as that of lncRNA 340 , 341 . The analysis of SARS-CoV-infected bronchoalveolar stem cells identified multiple deregulated miRNAs capable of interacting with both host and viral RNAs to create a pro-viral environment and escape immune recognition 342 .…”