Epitranscriptomic(N6-methyladenosine) Modification of Viral RNA and Virus-Host Interactions

Abstract

N6-methyladenosine (m⁶A) is the most prevalent and internal modification of eukaryotic mRNA. Multiple m⁶A methylation sites have been identified in the viral RNA genome and transcripts of DNA viruses in recent years. m⁶A modification is involved in all the phases of RNA metabolism, including RNA stability, splicing, nuclear exporting, RNA folding, translational modulation, and RNA degradation. Three protein groups, methyltransferases (m⁶A-writers), demethylases (m⁶A-erasers), and m⁶A-binding proteins (m⁶A-readers) regulate this dynamic reversible process. Here, we have reviewed the role of m⁶A modification dictating viral replication, morphogenesis, life cycle, and its contribution to disease progression. A better understanding of the m⁶A methylation process during viral pathogenesis is required to reveal novel approaches to combat the virus-associated diseases.

Keywords: m6A modification; m6A-binding protein; m6A-eraser; m6A-writer; viral epitranscriptomics.

Figure 1

Cellular m⁶A machinery: Writers, Erasers and Readers. Writer complex is composed of core subunits METTL3 and METTL14 with some additional adaptor proteins. METTL16 is also known as writer. Erasers: FTO and ALKBH5 are the known m⁶A erasers. Readers: YTH-domain containing proteins (YTHDF1-3, YTHDC1-2) directly recognize m⁶A- containing RNAs. A local structure disrupted by the presence of m⁶A could favor RNA-binding events of several heterogeneous nuclear ribonucleoproteins including HNRNPC/G and HNRNPA2B1. RNA binding proteins including IGF2BP1-3 and FMR1 prefer m⁶A-modified RNAs.