GSE128753
Herpes Simplex Virus blocks host transcription termination via the bimodal activities of ICP27.
Infection by viruses, including Herpes Simplex virus-1 (HSV-1), and cellular stresses cause widespread disruption of transcription termination (DoTT) of RNA polymerase II (RNAPII). The underlying mechanisms, however, remain unclear. Here we demonstrate that, in HSV-1-infected cells, the viral immediate early factor ICP27 is necessary and sufficient for inducing DoTT. Mechanistically, ICP27 directly binds to the essential mRNA 3' processing factor CPSF, induces the assembly of a dead-end 3' processing complex, and blocks mRNA cleavage. Remarkably, ICP27 also acts as a sequence-dependent activator of mRNA 3' processing for HSV-1 and a subset of host genes. Our results suggest that the bimodal activities of ICP27 play a key role in HSV-1-induced host shutoff and that CPSF is a common host factor targeted by multiple viruses. The mechanism described here may have implications for understanding other virus- and cell stress-mediated regulation of transcription termination. Overall design: (1) 4SU-seq: explore the effect of ICP27 and HSV-1 on transcription termination; (2) CLIP-seq: examination of RNA binding sites of ICP27.