• Herpes simplex virus blocks host transcription termination via the bimodal activities of ICP27.

      Wang, Xiuye; Hennig, Thomas; Whisnant, Adam W; Erhard, Florian; Prusty, Bhupesh K; Friedel, Caroline C; Forouzmand, Elmira; Hu, William; Erber, Luke; Chen, Yue; et al. (Nature publishing group, 2020-01-15)
      Infection by viruses, including herpes simplex virus-1 (HSV-1), and cellular stresses causewidespread disruption of transcription termination (DoTT) of RNA polymerase II (RNAPII) inhost genes. However, the underlying mechanisms remain unclear. Here, we demonstrate thatthe HSV-1 immediate early protein ICP27 induces DoTT by directly binding to the essentialmRNA 3’processing factor CPSF. It thereby induces the assembly of a dead-end 3’processing complex, blocking mRNA 3’cleavage. Remarkably, ICP27 also acts as a sequence-dependent activator of mRNA 3’processing for viral and a subset of host transcripts.Our results unravel a bimodal activity of ICP27 that plays a key role in HSV-1-induced hostshutoff and identify CPSF as an important factor that mediates regulation of transcriptiontermination. Thesefindings have broad implications for understanding the regulation oftranscription termination by other viruses, cellular stress and cancer.