Cap-specific terminal N6-methyladeonsine methylation of RNA mediated by PCIF1 and possible therapeutic implications

Posttranscriptional RNA modification is an important mode of epigenetic regulation in various biological and pathological contexts. N6, 2'-O-dimethyladenosine (m6Am) is one of the most abundant methylation modifications in mammals and usually occurs at the first transcribed nucleotide. Accumulating evidence indicates that m6Am modifications have important roles in RNA metabolism and physiological and pathological processes. PCIF1 (phosphorylated C-terminal domain interacting factor 1) is a protein that can bind to the phosphorylated C-terminal domain of RNA polymerase II through its WW domain. PCIF1 is named after this binding ability. Recently, PCIF1 has been identified as a cap-specific adenine N6-methyltransferase responsible for m6Am formation. Discovered as the sole m6Am methyltransferase for mammalian mRNA, PCIF1 has since received more extensive and in-depth study. Dysregulation of PCIF1 contributes to various pathological processes. Targeting PCIF1 may hold promising therapeutic significance. In this review, we provide an overview of the current knowledge of PCIF1. We explore the current understanding of the structure and the biological characteristics of PCIF1. We further review the molecular mechanisms of PCIF1 in cancer and viral infection and discuss its therapeutic potential.