RNA epitranscriptomics: Regulation of infection of RNA and DNA viruses by N6-methyladenosine (m6A)

Abstract

N6-methyladenosine (m6A) was discovered 4 decades ago. However, the functions of m6A and the cellular machinery that regulates its changes have just been revealed in the last few years. m6A is an abundant internal mRNA modification on cellular RNA and is implicated in diverse cellular functions. Recent works have demonstrated the presence of m6A 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 m6A “writers,” “erasers,” “readers,” and “antireaders” as well as the role of m6A in mRNA metabolism. We then review how the replications of numerous viruses are enhanced and restricted by m6A with emphasis on the oncogenic DNA virus, Kaposi sarcoma–associated herpesvirus (KSHV), whose m6A epitranscriptome was recently mapped. In the context of KSHV, m6A and the reader protein YTHDF2 acts as an antiviral mechanism during viral lytic replication. During viral latency, KSHV alters m6A 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 m6A in KSHV latent and lytic replication and KSHV-induced oncogenesis.