Dataset Information

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

ABSTRACT: 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) in host genes. However, the underlying mechanisms remain unclear. Here, we demonstrate that the HSV-1 immediate early protein ICP27 induces DoTT by directly binding to the essential mRNA 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 host shutoff and identify CPSF as an important factor that mediates regulation of transcription termination. These findings have broad implications for understanding the regulation of transcription termination by other viruses, cellular stress and cancer.

SUBMITTER: Wang X

PROVIDER: S-EPMC6962326 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Wang Xiuye X Hennig Thomas T Whisnant Adam W AW Erhard Florian F Prusty Bhupesh K BK Friedel Caroline C CC Forouzmand Elmira E Hu William W Erber Luke L Chen Yue Y Sandri-Goldin Rozanne M RM Dölken Lars L Shi Yongsheng Y

Nature communications 20200115 1

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) in host genes. However, the underlying mechanisms remain unclear. Here, we demonstrate that the HSV-1 immediate early protein ICP27 induces DoTT by directly binding to the essential mRNA 3' processing factor CPSF. It thereby induces the assembly of a dead-end 3' processing complex, blocking mRNA 3' cleavage. Remarkably ...[more]

PMID: 31941886

Similar Datasets

Project description:UnlabelledHerpesviruses are nuclear-replicating viruses that have successfully evolved to evade the immune system of humans, establishing lifelong infections. ICP27 from herpes simplex virus is a multifunctional regulatory protein that is functionally conserved in all known human herpesviruses. It has the potential to interact with an array of cellular proteins, as well as intronless viral RNAs. ICP27 plays an essential role in viral transcription, nuclear export of intronless RNAs, translation of viral transcripts, and virion host shutoff function. It has also been implicated in several signaling pathways and the prevention of apoptosis. Although much is known about its central role in viral replication and infection, very little is known about the structure and mechanistic properties of ICP27 and its homologs. We present the first crystal structure of ICP27 C-terminal domain at a resolution of 2.0 Å. The structure reveals the C-terminal half of ICP27 to have a novel fold consisting of α-helices and long loops, along with a unique CHCC-type of zinc-binding motif. The two termini of this domain extend from the central core and hint to possibilities of making interactions. ICP27 essential domain is capable of forming self-dimers as seen in the structure, which is confirmed by analytical ultracentrifugation study. Preliminary in vitro phosphorylation assays reveal that this domain may be regulated by cellular kinases.ImportanceICP27 is a key regulatory protein of the herpes simplex virus and has functional homologs in all known human herpesviruses. Understanding the structure of this protein is a step ahead in deciphering the mechanism by which the virus thrives. In this study, we present the first structure of the C-terminal domain of ICP27 and describe its novel features. We critically analyze the structure and compare our results to the information available form earlier studies. This structure can act as a guide in future experimental designs and can add to a better understanding of mechanism of ICP27, as well as that of its homologs.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets