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

Xiuye Wang; Thomas Hennig; Adam W Whisnant; Florian Erhard; Bhupesh K Prusty; Caroline C Friedel; Elmira Forouzmand; William Hu; Luke Erber; Yue Chen; Rozanne M Sandri-Goldin; Lars Dölken; Yongsheng Shi

doi:10.1038/s41467-019-14109-x

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

Xiuye Wang, Thomas Hennig, Adam W Whisnant, Florian Erhard, Bhupesh K Prusty, Caroline C Friedel, Elmira Forouzmand, William Hu, Luke Erber, Yue Chen, Rozanne M Sandri-Goldin (Corresponding Author), Lars Dölken (Corresponding Author), Yongsheng Shi (Corresponding Author)

Research output: Contribution to journal › Article › peer-review

57 Citations (Scopus)

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.

Original language	English
Article number	293
Pages (from-to)	1-13
Number of pages	13
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-14109-x
Publication status	Published - 15 Jan 2020
Externally published	Yes

Keywords*

Animals
Cell Line
Cleavage And Polyadenylation Specificity Factor/metabolism
HeLa Cells
Herpes Simplex/genetics
Herpesvirus 1, Human/genetics
Host-Pathogen Interactions/genetics
Humans
Immediate-Early Proteins/genetics
RNA Processing, Post-Transcriptional
RNA, Messenger/genetics
Transcription Termination, Genetic

Field of Science*

1.6 Biological sciences
3.1 Basic medicine
3.3 Health sciences

Publication Type*

1.1. Scientific article indexed in Web of Science and/or Scopus database

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41467-019-14109-x

Cite this

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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.",

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author = "Xiuye Wang and Thomas Hennig and Whisnant, {Adam W} and Florian Erhard and Prusty, {Bhupesh K} and Friedel, {Caroline C} and Elmira Forouzmand and William Hu and Luke Erber and Yue Chen and Sandri-Goldin, {Rozanne M} and Lars D{\"o}lken and Yongsheng Shi",

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doi = "10.1038/s41467-019-14109-x",

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AU - Wang, Xiuye

AU - Hennig, Thomas

AU - Whisnant, Adam W

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AU - Prusty, Bhupesh K

AU - Friedel, Caroline C

AU - Forouzmand, Elmira

AU - Hu, William

AU - Erber, Luke

AU - Chen, Yue

AU - Sandri-Goldin, Rozanne M

AU - Dölken, Lars

AU - Shi, Yongsheng

PY - 2020/1/15

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N2 - 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.

AB - 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.

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KW - Immediate-Early Proteins/genetics

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

Abstract

Keywords*

Field of Science*

Publication Type*

UN SDGs

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