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The RNA quality control pathway nonsense-mediated mRNA decay targets cellular and viral RNAs to restrict KSHV.
- Source :
-
Nature communications [Nat Commun] 2020 Jul 03; Vol. 11 (1), pp. 3345. Date of Electronic Publication: 2020 Jul 03. - Publication Year :
- 2020
-
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.
- Subjects :
- Cell Line, Tumor
HEK293 Cells
Herpesvirus 8, Human metabolism
Herpesvirus 8, Human pathogenicity
Host-Pathogen Interactions genetics
Humans
Immediate-Early Proteins genetics
Immediate-Early Proteins metabolism
Lymphoma, Primary Effusion genetics
Lymphoma, Primary Effusion virology
RNA, Messenger metabolism
RNA-Seq
Sarcoma, Kaposi genetics
Sarcoma, Kaposi virology
Trans-Activators genetics
Trans-Activators metabolism
Transcriptional Activation
Unfolded Protein Response genetics
Virus Latency genetics
Gene Expression Regulation, Viral
Herpesvirus 8, Human genetics
Nonsense Mediated mRNA Decay
RNA, Viral metabolism
Virus Activation genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 32620802
- Full Text :
- https://doi.org/10.1038/s41467-020-17151-2