Emerging Roles of N(6)-Methyladenosine on HIV-1 RNA Metabolism and Viral Replication

N(6)-methyladenosine (m(6)A) is the most abundant internal modification present in Eukaryotic mRNA. The functions of this chemical modification are mediated by m(6)A-binding proteins (m(6)A readers) and regulated by methyltransferases (m(6)A writers) and demethylases (m(6)A erasers), which together are proposed to be responsible of a new layer of post-transcriptional control of gene expression. Despite the presence of m(6)A in a retroviral genome was reported more than 40 years ago, the recent development of sequencing-based technologies allowing the mapping of m(6)A in a transcriptome-wide manner made it possible to identify the topology and dynamics of m(6)A during replication of HIV-1 as well as other viruses. As such, three independent groups recently reported the presence of m(6)A along the HIV-1 genomic RNA (gRNA) and described the impact of cellular m(6)A writers, erasers and readers on different steps of viral RNA metabolism and replication. Interestingly, while two groups reported a positive role of m(6)A at different steps of viral gene expression it was also proposed that the presence of m(6)A within the gRNA reduces viral infectivity by inducing the early degradation of the incoming viral genome. This review summarizes the recent advances in this emerging field and discusses the relevance of m(6)A during HIV-1 replication.