Mechanism and consequences of herpes simplex virus 1-mediated regulation of host mRNA alternative polyadenylation

Herpes Simplex virus-1 (HSV-1) causes widespread disruption of transcription termination (DoTT) of RNA polymerase II (RNAPII) mainly by immediate early gene ICP27. Mechanistically, ICP27 directly binds to the essential mRNA 3’ processingfactor 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 here show that the bimodal activities of ICP27 play a key role in HSV-1-induced alternative polyadenyalation. (1) 4SU-seq: explore the effect of ICP27 and HSV-1 on transcription termination; (2) CLIP-seq: examination of RNA binding sites of ICP27.