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

Abstract

Background In recent years, accumulating evidences have revealed that influenza A virus (IAV) infections induce significant differential expression of host long noncoding RNAs (lncRNAs), some of which play important roles in the regulation of virus-host interactions and determining the virus pathogenesis. However, whether these lncRNAs bear post-translational modifications and how their differential expression is regulated remain largely unknown. In this study, the transcriptome-wide 5-methylcytosine (m5C) modification of lncRNAs in A549 cells infected with an H1N1 influenza A virus was analyzed and compared with uninfected cells by Methylated RNA immunoprecipitation sequencing (MeRIP-Seq). Results Our data identified 1317 upregulated m5C peaks and 1667 downregulated peaks in the H1N1 infected group. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the differentially modified lncRNAs were associated with protein modification, organelle localization, nuclear export and other biological processes. Furthermore, conjoint analysis of the differentially modified (DM) and differentially expressed (DE) lncRNAs identified 143 ‘hyper-up’, 81 ‘hypo-up’, 6 ‘hypo-down’ and 4 ‘hyper-down’ lncRNAs. GO and KEGG analyses revealed that these DM and DE lncRNAs were predominantly associated with pathogen recognition and disease pathogenesis pathways, indicating that m5C modifications could play an important role in the regulation of host response to IAV replication by modulating the expression and/or stability of lncRNAs. Conclusion This study presented the first m5C modification profile of lncRNAs in A549 cells infected with IAV and demonstrated a significant alteration of m5C modifications on host lncRNAs upon IAV infection. These data could give a reference to future researches on the roles of m5C methylation in virus infection.

The hidden RNA code: implications of the RNA epitranscriptome in the context of viral infections

“…Similarly, an hyperediting of the viral edited repeat-long (ERL) lncRNA occurred during MDV infection to downregulate IFN, particularly at the MDV lytic phase, and correlated with increased ADAR1 activity ( Figueroa et al, 2016 ). Recently, m 5 C peaks were identified, following IAV infection, in several host lncRNAs, mostly associated with immune recognition and disease pathogenesis, possibly to regulate host responses to IAV by influencing the expression and stability of specific lncRNAs ( Jiang et al, 2023 ) ( Figure 1B ).…”