Fig. 3. Epitranscriptomic modifications of viral RNA.

The indicated epitranscriptomic marks are N⁶-methyladenosine (m⁶A), 5-methylcytidine (m⁵C), N⁴-acetylcytidine (ac⁴C) and 2ʹO-methylated nucleosides (Nm), deposited respectively by a complex that includes the proteins METTL3, METTL14 and WTAP (among other cofactors), by NSUN2, by nuclear N-acetyltransferase 10 (NAT10) and by FTSJ3. All four of these epitranscriptomic marks have been reported to promote viral replication by affecting different steps in the viral replication cycle, either by upregulating viral mRNA stability or translation, or by preventing the detection of viral RNAs by host RNA-specific innate immunity factors, including RIG-I and MDA5. Of note, it is currently unknown whether RNA modifications have distinct functions when deposited on viral mRNA as opposed to viral RNA genomes, but this remains a possibility.