RNA epitranscriptomics: Regulation of infection of RNA and DNA viruses by N-6-methyladenosine (m(6)A)

N-6-methyladenosine (m(6)A) was discovered 4 decades ago. However, the functions of m(6)A and the cellular machinery that regulates its changes have just been revealed in the last few years. m(6)A is an abundant internal mRNA modification on cellular RNA and is implicated in diverse cellular functions. Recent works have demonstrated the presence of m(6)A in the genomes of RNA viruses and transcripts of a DNA virus with either a proviral or antiviral role. Here, we first summarize what is known about the m(6)A writers, erasers, readers, and antireaders as well as the role of m(6)A in mRNA metabolism. We then review how the replications of numerous viruses are enhanced and restricted by m(6)A with emphasis on the oncogenic DNA virus, Kaposi sarcoma-associated herpesvirus (KSHV), whose m(6)A epitranscriptome was recently mapped. In the context of KSHV, m(6)A and the reader protein YTHDF2 acts as an antiviral mechanism during viral lytic replication. During viral latency, KSHV alters m(6)A on genes that are implicated in cellular transformation and viral latency. Lastly, we discuss future studies that are important to further delineate the functions of m(6)A in KSHV latent and lytic replication and KSHV-induced oncogenesis.