Abstract
Epitranscriptomic RNA modifications play a crucial role in the posttranscriptional regulation of gene expression. N(6)-methyladenosine (m(6)A) is the most prevalent internal modification of eukaryotic RNA and plays a pivotal role in RNA fate. RNA m(6)A modification is regulated by a group of cellular proteins, methyltransferases (writers) and demethylases (erasers), which add and remove the methyl group from adenosine, respectively. m(6)A modification is recognized by a group of cellular RNA-binding proteins (readers) that specifically bind to m(6)A-modified RNA, mediating effects on RNA stability, splicing, transport, and translation. The functional significance of m(6)A modification of viral and cellular RNA is an active area of virology research. In this review, we summarize and analyze the current literature on m(6)A modification of HIV-1 RNA, the multifaceted functions of m(6)A in regulating HIV-1 replication, and the role of viral RNA m(6)A modification in evading innate immune responses to infection. Furthermore, we briefly discuss the future directions and therapeutic implications of mechanistic studies of HIV-1 epitranscriptomic modifications.