Widespread remodeling of the m <sup>6</sup> A RNA-modification landscape by a viral regulator of RNA processing and export
Kalanghad Puthankalam Srinivas, Daniel P. Depledge, Jonathan S. Abebe, Stephen A. Rice, Ian Mohr, Angus C. Wilson
Abstract
Significance Herpes simplex virus infections cause painful lesions, blindness, and viral encephalitis. At the cellular level, infection causes a dramatic shutdown of host gene expression, allowing the virus to monopolize the transcriptional and translational machinery. One of the viral proteins responsible is ICP27, which disrupts cellular RNA processing, leading to nuclear accumulation and accelerated turnover of aberrant pre-mRNAs. ICP27 also facilitates nucleocytoplasmic export of viral messenger RNAs (mRNAs). Recent studies establish that the RNA modification N 6 -methyladenosine (m 6 A) also regulates mRNA biogenesis, export, stability, and translation. Here, we show that the m 6 A pathway becomes progressively less important for viral gene expression as the infection cycle progresses and that ICP27 disrupts the m6A pathway through redistribution of nuclear methyltransferase components into the cytoplasm.