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, Lars Dölken, Yongsheng Shi

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

35 Scopus citations

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 (US)
Article number	293
Journal	Nature communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-14109-x
State	Published - Jan 15 2020

Bibliographical note

Funding Information:
We would like to thank David M. Knipe for providing reagents, Neal deLuca for providing his extended set of HSV-1 deletion mutants and UCI GHTF for sequencing. This study was supported by the following grants: NIH GM090056 and GM128441 to Y.S. ERC Consolidator award (ERC-2016-CoG 721016-HERPES) and DFG grant DFG (1275/6-1 to L.D.). A.W.W. was the recipient of a generous grant from the Alexander von Humboldt Foundation.

Publisher Copyright:
© 2020, The Author(s).

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

PubMed: MeSH publication types

Research Support, Non-U.S. Gov't
Journal Article
Research Support, N.I.H., Extramural

UN SDGs

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

Publisher link

10.1038/s41467-019-14109-x

Find It

Find It at U of M Libraries

Cite this

@article{74342422306b49d1ad8fd93601b6b2cf,

title = "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{\textquoteright} processing factor CPSF. It thereby induces the assembly of a dead-end 3{\textquoteright} processing complex, blocking mRNA 3{\textquoteright} cleavage. Remarkably, ICP27 also acts as a sequence-dependent activator of mRNA 3{\textquoteright} 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.",

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",

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",

note = "Funding Information: We would like to thank David M. Knipe for providing reagents, Neal deLuca for providing his extended set of HSV-1 deletion mutants and UCI GHTF for sequencing. This study was supported by the following grants: NIH GM090056 and GM128441 to Y.S. ERC Consolidator award (ERC-2016-CoG 721016-HERPES) and DFG grant DFG (1275/6-1 to L.D.). A.W.W. was the recipient of a generous grant from the Alexander von Humboldt Foundation. Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = jan,

day = "15",

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

language = "English (US)",

volume = "11",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Herpes simplex virus blocks host transcription termination via the bimodal activities of ICP27

AU - Wang, Xiuye

AU - Hennig, Thomas

AU - Whisnant, Adam W.

AU - Erhard, Florian

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

N1 - Funding Information: We would like to thank David M. Knipe for providing reagents, Neal deLuca for providing his extended set of HSV-1 deletion mutants and UCI GHTF for sequencing. This study was supported by the following grants: NIH GM090056 and GM128441 to Y.S. ERC Consolidator award (ERC-2016-CoG 721016-HERPES) and DFG grant DFG (1275/6-1 to L.D.). A.W.W. was the recipient of a generous grant from the Alexander von Humboldt Foundation. Publisher Copyright: © 2020, The Author(s).

PY - 2020/1/15

Y1 - 2020/1/15

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.

KW - Animals

KW - Cell Line

KW - Cleavage And Polyadenylation Specificity Factor/metabolism

KW - HeLa Cells

KW - Herpes Simplex/genetics

KW - Herpesvirus 1, Human/genetics

KW - Host-Pathogen Interactions/genetics

KW - Humans

KW - Immediate-Early Proteins/genetics

KW - RNA Processing, Post-Transcriptional

KW - RNA, Messenger/genetics

KW - Transcription Termination, Genetic

UR - http://www.scopus.com/inward/record.url?scp=85077942163&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85077942163&partnerID=8YFLogxK

U2 - 10.1038/s41467-019-14109-x

DO - 10.1038/s41467-019-14109-x

M3 - Article

C2 - 31941886

AN - SCOPUS:85077942163

SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 293

ER -

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

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

UN SDGs

Publisher link

Find It

Other files and links

Fingerprint

Cite this