m6A modification landscapes of human metapneumovirus, mumps virus, and host A549 cell RNAs revealed by single-base-resolution GLORI-seq [A549 GLORI]

Multiple viruses exploit host m6A machinery to modify their own genomic RNA and mRNA, thereby facilitating viral replication and evasion of host innate immune surveillance. In this study, we employed the single-base-resolution high-throughput sequencing technique glyoxal and nitrite-mediated deamination of unmethylated adenosines (GLORI) to identify m6A modification sites on the RNAs of Human metapneumovirus (hMPV, NL/1/00 strain) and Mumps virus (MuV, JL2 strain), as well as to characterize the m6A landscapes of the host cell transcriptome in A549 lung epithelial cells.

Extensive m6A modifications on viral RNAs exhibited dynamic and gene-specific distributions, while viral infection significantly reprogrammed the m6A landscape of A549 cells, including increased m6A modification in multiple innate immune signaling pathways. Furthermore, through integrated transcriptomic analyses and modulation of host m6A machinery levels, we demonstrated the dual regulatory roles of m6A in both viral replication and host immune responses.