ArticleProceedings of the National Academy of Sciences of the United States of America2015
Virus-induced translational arrest through 4EBP1/2-dependent decay of 5'-TOP mRNAs restricts viral infection.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 51 citations in OpenAlex.
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- Nutrient-driven TOR signalling controls a chromatin-associated complex for orchestrating plant growth and stress tolerance.Nature plants · 2025Article
- Structural snapshots of phenuivirus cap-snatching and transcription.Nucleic acids research · 2024Article
- An LIR motif in the Rift Valley fever virus NSs protein is critical for the interaction with LC3 family members and inhibition of autophagy.PLoS pathogens · 2024Article
- RNA to Rule Them All: Critical Steps in Lassa Virus Ribonucleoparticle Assembly and Recruitment.Journal of the American Chemical Society · 2023Article
- Multiple functions of stress granules in viral infection at a glance.Frontiers in microbiology · 2023Review
- Natural hosts and animal models for Rift Valley fever phlebovirus.Frontiers in veterinary science · 2023Review
- White spot syndrome virus directly activates mTORC1 signaling to facilitate its replication via polymeric immunoglobulin receptor-mediated infection in shrimp.PLoS pathogens · 2022Article
- The cap-snatching frequency of a plant bunyavirus from nonsense mRNAs is low but is increased by silencing of UPF1 or SMG7.Molecular plant pathology · 2022Article
- Transcriptomic profile investigations highlight a putative role for NUDT16 in sepsis.Journal of cellular and molecular medicine · 2022Article
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- Perturbation of nuclear-cytosolic shuttling of Rx1 compromises extreme resistance and translational arrest of potato virus X transcripts.The Plant journal : for cell and molecular biology · 2021Article
- LARP1 and LARP4: up close with PABP for mRNA 3' poly(A) protection and stabilization.RNA biology · 2021Review
- The isolated La-module of LARP1 mediates 3' poly(A) protection and mRNA stabilization, dependent on its intrinsic PAM2 binding to PABPC1.RNA biology · 2021Article
- Viral Regulation of RNA Granules in Infected Cells.Virologica Sinica · 2019Review
- Strategies for Success. Viral Infections and Membraneless Organelles.Frontiers in cellular and infection microbiology · 2019Review
- Transcriptome profiling in Rift Valley fever virus infected cells reveals modified transcriptional and alternative splicing programs.PloS one · 2019Article
- Viral-Mediated mRNA Degradation for Pathogenesis.Biomedicines · 2018Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The mosquito-transmitted bunyavirus, Rift Valley fever virus (RVFV), is a highly successful pathogen for which there are no vaccines or therapeutics. Translational arrest is a common antiviral strategy used by hosts. In response, RVFV inhibits two well-known antiviral pathways that attenuate translation during infection, PKR and type I IFN signaling. Despite this, translational arrest occurs during RVFV infection by unknown mechanisms. Here, we find that RVFV infection triggers the decay of core translation machinery mRNAs that possess a 5'-terminal oligopyrimidine (5'-TOP) motif in their 5'-UTR, including mRNAs encoding ribosomal proteins, which leads to a decrease in overall ribosomal protein levels. We find that the RNA decapping enzyme NUDT16 selectively degrades 5'-TOP mRNAs during RVFV infection and this decay is triggered in response to mTOR attenuation via the translational repressor 4EBP1/2 axis. Translational arrest of 5'-TOPs via 4EBP1/2 restricts RVFV replication, and this increased RNA decay results in the loss of visible RNA granules, including P bodies and stress granules. Because RVFV cap-snatches in RNA granules, the increased level of 5'-TOP mRNAs in this compartment leads to snatching of these targets, which are translationally suppressed during infection. Therefore, translation of RVFV mRNAs is compromised by multiple mechanisms during infection. Together, these data present a previously unknown mechanism for translational shutdown in response to viral infection and identify mTOR attenuation as a potential therapeutic avenue against bunyaviral infection.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.