The RNA quality control pathway nonsense-mediated mRNA decay targets cellular and viral RNAs to restrict KSHV
Yang Zhao,
Xiang Ye,
Myriam Shehata,
William Dunker,
Zhihang Xie and
John Karijolich ()
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Yang Zhao: Vanderbilt University Medical Center
Xiang Ye: Vanderbilt University Medical Center
Myriam Shehata: Vanderbilt University Medical Center
William Dunker: Vanderbilt University Medical Center
Zhihang Xie: Vanderbilt University Medical Center
John Karijolich: Vanderbilt University Medical Center
Nature Communications, 2020, vol. 11, issue 1, 1-15
Abstract:
Abstract Nonsense-mediated mRNA decay (NMD) is an evolutionarily conserved RNA decay mechanism that has emerged as a potent cell-intrinsic restriction mechanism of retroviruses and positive-strand RNA viruses. However, whether NMD is capable of restricting DNA viruses is not known. The DNA virus Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi’s sarcoma and primary effusion lymphoma (PEL). Here, we demonstrate that NMD restricts KSHV lytic reactivation. Leveraging high-throughput transcriptomics we identify NMD targets transcriptome-wide in PEL cells and identify host and viral RNAs as substrates. Moreover, we identified an NMD-regulated link between activation of the unfolded protein response and transcriptional activation of the main KSHV transcription factor RTA, itself an NMD target. Collectively, our study describes an intricate relationship between cellular targets of an RNA quality control pathway and KSHV lytic gene expression, and demonstrates that NMD can function as a cell intrinsic restriction mechanism acting upon DNA viruses.
Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17151-2
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DOI: 10.1038/s41467-020-17151-2
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