A Herpesvirus Protein Selectively Inhibits Cellular mRNA Nuclear Export

Publication date: 9 November 2016
Source:Cell Host & Microbe, Volume 20, Issue 5
Author(s): 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
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.

Graphical abstract

Teaser

Viruses have evolved multiple mechanisms to inhibit cellular gene expression, thereby impeding host antiviral responses. Gong et al. identify a herpesvirus protein, ORF10, of KSHV that blocks nuclear export of selective mRNAs by interacting with an RNA export factor, Rae1. This interaction of ORF10 is critical for optimal KSHV replication.


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