A Herpesvirus Protein Selectively Inhibits Cellular mRNA Nuclear Export

Danyang Gong; Yong Hoon Kim; Yuchen Xiao; Yushen Du; Yafang Xie; Kevin K Lee; Jun Feng; Nisar Farhat; Dawei Zhao; Sara Shu; Xinghong Dai; Sumit K Chanda; Tariq M Rana; Nevan J Krogan; Ren Sun; Ting-Ting Wu

doi:10.1016/j.chom.2016.10.004

A Herpesvirus Protein Selectively Inhibits Cellular mRNA Nuclear Export

Cell Host Microbe. 2016 Nov 9;20(5):642-653. doi: 10.1016/j.chom.2016.10.004.

Authors

Danyang Gong¹, Yong Hoon Kim¹, Yuchen Xiao², Yushen Du¹, Yafang Xie¹, Kevin K Lee³, Jun Feng¹, Nisar Farhat¹, Dawei Zhao¹, Sara Shu¹, Xinghong Dai¹, Sumit K Chanda⁴, Tariq M Rana⁵, Nevan J Krogan⁶, Ren Sun¹, Ting-Ting Wu⁷

Affiliations

¹ Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
² Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
³ School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁴ Infectious and Inflammatory Disease Center, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
⁵ Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA.
⁶ Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
⁷ Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: twu@mednet.ucla.edu.

Abstract

Nuclear mRNA export is highly regulated to ensure accurate cellular gene expression. Viral inhibition of cellular mRNA export can enhance viral access to the cellular translation machinery and prevent anti-viral protein production but is generally thought to be nonselective. We report that ORF10 of Kaposi's sarcoma-associated herpesvirus (KSHV), a nuclear DNA virus, inhibits mRNA export in a transcript-selective manner to control cellular gene expression. Nuclear export inhibition by ORF10 requires an interaction with an RNA export factor, Rae1. Genome-wide analysis reveals a subset of cellular mRNAs whose nuclear export is blocked by ORF10 with the 3' UTRs of ORF10-targeted transcripts conferring sensitivity to export inhibition. The ORF10-Rae1 interaction is important for the virus to express viral genes and produce infectious virions. These results suggest that a nuclear DNA virus can selectively interfere with RNA export to restrict host gene expression for optimal replication.

Keywords: 3′ UTR; KSHV; Nup98; ORF10; Rae1; herpesvirus; late gene; mRNA nuclear export.

Published by Elsevier Inc.

MeSH terms

Active Transport, Cell Nucleus*
Animals
Cell Line
Gene Expression Regulation
Herpesvirus 8, Human / physiology*
Host-Pathogen Interactions*
Humans
Models, Biological
Nuclear Matrix-Associated Proteins / metabolism*
Nucleocytoplasmic Transport Proteins / metabolism*
Protein Binding
RNA, Messenger / metabolism*
Viral Proteins / metabolism*
Virus Replication*

Substances

Nuclear Matrix-Associated Proteins
Nucleocytoplasmic Transport Proteins
RAE1 protein, human
RNA, Messenger
Viral Proteins

Abstract

MeSH terms

Substances

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