College of Life Sciences, Northwest A & F University, Yangling, 712100, Shanxi, P. R. China.
School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, 442000, Hubei, P. R. China.
BMC Genomics. 2023 Jun 12;24(1):316. doi: 10.1186/s12864-023-09432-z.
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 (mC) 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).
Our data identified 1317 upregulated mC 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 mC modifications could play an important role in the regulation of host response to IAV replication by modulating the expression and/or stability of lncRNAs.
This study presented the first mC modification profile of lncRNAs in A549 cells infected with IAV and demonstrated a significant alteration of mC modifications on host lncRNAs upon IAV infection. These data could give a reference to future researches on the roles of mC methylation in virus infection.
近年来,越来越多的证据表明甲型流感病毒(IAV)感染会诱导宿主长非编码 RNA(lncRNA)的显著差异表达,其中一些在调节病毒-宿主相互作用和决定病毒发病机制方面发挥着重要作用。然而,这些 lncRNA 是否存在翻译后修饰以及它们的差异表达是如何调控的,在很大程度上仍然未知。在这项研究中,通过甲基化 RNA 免疫沉淀测序(MeRIP-Seq)分析了甲型流感病毒感染 A549 细胞后 lncRNA 的全转录组 5-甲基胞嘧啶(mC)修饰,并与未感染细胞进行了比较。
我们的数据在 H1N1 感染组中鉴定出 1317 个上调的 mC 峰和 1667 个下调的 mC 峰。基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析表明,差异修饰的 lncRNA 与蛋白质修饰、细胞器定位、核输出等生物学过程有关。此外,差异修饰(DM)和差异表达(DE)lncRNA 的联合分析鉴定出 143 个“高上调”、81 个“低上调”、6 个“低下调”和 4 个“高下调”lncRNA。GO 和 KEGG 分析表明,这些 DM 和 DE lncRNA 主要与病原体识别和疾病发病机制途径有关,这表明 mC 修饰可能通过调节 lncRNA 的表达和/或稳定性,在宿主对 IAV 复制的反应调控中发挥重要作用。
本研究首次报道了 IAV 感染 A549 细胞后 lncRNA 的 mC 修饰谱,并证实了 IAV 感染后宿主 lncRNA 的 mC 修饰发生了显著改变。这些数据为今后研究 mC 甲基化在病毒感染中的作用提供了参考。