The RNA Epitranscriptome of DNA Viruses

Abstract

RNA modifications have generated much interest in the virology field, as recent works have shown that many viruses harbor these marks and modify cellular marks. The most abundant mRNA modification in eukaryotic cells, N⁶-methyladenosine (m⁶A), has been examined extensively at the genome-wide scale in both cellular and viral contexts. This Gem discusses the role of m⁶A in gene regulation and describes recent advancements in Kaposi's sarcoma-associated herpesvirus (KSHV) and simian virus 40 (SV40) research. We provide insights into future research related to m⁶A in DNA viruses.

Keywords: 3′UTR hypermethylation; 5′UTR hypomethylation; KSHV; Kaposi's sarcoma-associated herpesvirus; N6,2′-O-dimethyladenosine; N6-methyladenosine; SV40; YTHDC1; YTHDF2; epitranscriptome; latency and lytic replication; m6A; m6Am; simian virus 40.

FIG 1

(A) KSHV reprograms the cellular epitranscriptome during latency, causing 5′UTR hypomethylation and 3′UTR hypermethylation (89). (B) Regulation of SV40 and KSHV replication by m⁶A. The influence of m⁶A on key events during SV40 and KSHV viral replication is highlighted. In the nucleus, the methyltransferases METTL3 and METTL14 favor the accumulation of SV40 and KSHV transcripts (90, 92). YTHDC1 enhances splicing of KSHV RTA transcripts (92). In the cytoplasm, YTHDF2 mediates degradation of KSHV transcripts, leading to repression of viral replication (89). YTHDF2 and YTHDF3 promote viral replication in KSHV (90) and SV40 (63), through a noncanonical role of these proteins.