Attacked from All Sides: RNA Decay in Antiviral Defense

The innate immune system has evolved a number of sensors that recognize viral RNA (vRNA) to restrict infection, yet the full spectrum of host-encoded RNA binding proteins that target these foreign RNAs is still unknown. The RNA decay machinery, which uses exonucleases to degrade aberrant RNAs largely from the 5′ or 3′ end, is increasingly recognized as playing an important role in antiviral defense. The 5′ degradation pathway can directly target viral messenger RNA (mRNA) for degradation, as well as indirectly attenuate replication by limiting specific pools of endogenous RNAs. The 3′ degradation machinery (RNA exosome) is emerging as a downstream effector of a diverse array of vRNA sensors. This review discusses our current understanding of the roles of the RNA decay machinery in controlling viral infection.

• Publication year

  2017

• Venue

  Viruses

• Publication date

  2017-01-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3390/v9010002PMID 28054965PMCID 5294971
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Mutations in the G-domain of Ski7 cause specific dysfunction in non-stop decay

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• NSs Virulence Factor of Rift Valley Fever Virus Engages the F-Box Proteins FBXW11 and β-TRCP1 To Degrade the Antiviral Protein Kinase PKR

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• A conserved virus-induced cytoplasmic TRAMP-like complex recruits the exosome to target viral RNA for degradation

  2016cited by this paper
• The Exosome Is Recruited to RNA Substrates through Specific Adaptor Proteins.

  2015cited by this paper
• P-body assembly requires DDX6 repression complexes rather than decay or Ataxin2/2L complexes

  2015cited by this paper
• Apoptosis Triggers Specific, Rapid, and Global mRNA Decay with 3′ Uridylated Intermediates Degraded by DIS3L2

  2015cited by this paper
• TGF-β Suppression of HBV RNA through AID-Dependent Recruitment of an RNA Exosome Complex

  2015cited by this paper
• Virus-induced translational arrest through 4EBP1/2-dependent decay of 5′-TOP mRNAs restricts viral infection

  2015influential reference
• The human nuclear exosome targeting complex is loaded onto newly synthesized RNA to direct early ribonucleolysis.

  2015cited by this paper
• A combined proteomics/genomics approach links hepatitis C virus infection with nonsense-mediated mRNA decay.

  2015cited by this paper
• The host nonsense-mediated mRNA decay pathway restricts Mammalian RNA virus replication.

  2014cited by this paper
• The innate immune sensor LGP2 activates antiviral signaling by regulating MDA5-RNA interaction and filament assembly.

  2014cited by this paper
• Hippo signaling regulates microprocessor and links cell-density-dependent miRNA biogenesis to cancer.

  2014cited by this paper
• The cGAS-cGAMP-STING pathway of cytosolic DNA sensing and signaling.

  2014cited by this paper
• Certain Adenylated Non-Coding RNAs, Including 5′ Leader Sequences of Primary MicroRNA Transcripts, Accumulate in Mouse Cells following Depletion of the RNA Helicase MTR4

  2014cited by this paper
• The SKIV2L RNA exosome limits activation of the RIG-I-like receptors

  2014cited by this paper
• Nonsense-Mediated Decay Serves as a General Viral Restriction Mechanism in Plants

  2014influential reference
• Drosha as an interferon-independent antiviral factor

  2014cited by this paper
• RNase-L Control of Cellular mRNAs: Roles in Biologic Functions and Mechanisms of Substrate Targeting

  2014cited by this paper
• Stem-loop recognition by DDX17 facilitates miRNA processing and antiviral defense.

  2014cited by this paper
• A genome-wide RNAi screen reveals that mRNA decapping restricts bunyaviral replication by limiting the pools of Dcp2-accessible targets for cap-snatching.

  2013cited by this paper
• Mammalian DIS3L2 exoribonuclease targets the uridylated precursors of let-7 miRNAs

  2013cited by this paper
• P-body components LSM1, GW182, DDX3, DDX6 and XRN1 are recruited to WNV replication sites and positively regulate viral replication.

  2013cited by this paper
• Threading the barrel of the RNA exosome

  2013cited by this paper
• A role for the Perlman syndrome exonuclease Dis3l2 in the Lin28-let-7 pathway

  2013cited by this paper
• Crystal structure of an RNA-bound 11-subunit eukaryotic exosome complex

  2013cited by this paper
• Viral interference with host mRNA surveillance, the nonsense-mediated mRNA decay (NMD) pathway, through a new function of HTLV-1 Rex: implications for retroviral replication.

  2013cited by this paper
• Cytoplasmic Viruses: Rage against the (Cellular RNA Decay) Machine

  2013cited by this paper
• The human cap-binding complex is functionally connected to the nuclear RNA exosome

  2013cited by this paper
• Nuclease Activity of the Human SAMHD1 Protein Implicated in the Aicardi-Goutières Syndrome and HIV-1 Restriction*

  2013cited by this paper
• Inhibition and avoidance of mRNA degradation by RNA viruses.

  2012cited by this paper
• A noncoding RNA produced by arthropod-borne flaviviruses inhibits the cellular exoribonuclease XRN1 and alters host mRNA stability.

  2012cited by this paper
• ATP Hydrolysis Enhances RNA Recognition and Antiviral Signal Transduction by the Innate Immune Sensor, Laboratory of Genetics and Physiology 2 (LGP2)*

  2012cited by this paper
• Air proteins control differential TRAMP substrate specificity for nuclear RNA surveillance.

  2012cited by this paper
• Toll‐like receptor (TLR) 3 immune modulation by unformulated small interfering RNA or DNA and the role of CD14 (in TLR‐mediated effects)

  2012cited by this paper
• Poly(A)-Binding Protein Facilitates Translation of an Uncapped/Nonpolyadenylated Viral RNA by Binding to the 3′ Untranslated Region

  2012cited by this paper
• mRNA decapping factors and the exonuclease Xrn2 function in widespread premature termination of RNA polymerase II transcription.

  2012cited by this paper
• Sensing of RNA Viruses: a Review of Innate Immune Receptors Involved in Recognizing RNA Virus Invasion

  2012cited by this paper
• Adeno-Associated Virus Activates an Innate Immune Response in Normal Human Cells but Not in Osteosarcoma Cells

  2011cited by this paper
• The Early Interferon Response to Rotavirus Is Regulated by PKR and Depends on MAVS/IPS-1, RIG-I, MDA-5, and IRF3

  2011cited by this paper
• SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx

  2011cited by this paper
• Characterizing mRNA Interactions with RNA Granules during Translation Initiation Inhibition

  2011cited by this paper
• Zinc-finger antiviral protein inhibits HIV-1 infection by selectively targeting multiply spliced viral mRNAs for degradation

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• DDX60, a DEXD/H Box Helicase, Is a Novel Antiviral Factor Promoting RIG-I-Like Receptor-Mediated Signaling

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• Air1 Zinc Knuckles 4 and 5 and a Conserved IWRXY Motif Are Critical for the Function and Integrity of the Trf4/5-Air1/2-Mtr4 Polyadenylation (TRAMP) RNA Quality Control Complex*

  2011cited by this paper
• Aicardi-Goutières Syndrome Gene and HIV-1 Restriction Factor SAMHD1 Is a dGTP-regulated Deoxynucleotide Triphosphohydrolase*♦

  2011influential reference
• Nucleic acid recognition by the innate immune system.

  2011cited by this paper
• eIF2A mediates translation of hepatitis C viral mRNA under stress conditions

  2011cited by this paper
• Quantitative mass spectrometry of DENV-2 RNA-interacting proteins reveals that the DEAD-box RNA helicase DDX6 binds the DB1 and DB2 3’ UTR structures

  2011cited by this paper
• Conventional and unconventional mechanisms for capping viral mRNA

  2011cited by this paper
• Interaction profiling identifies the human nuclear exosome targeting complex.

  2011influential reference
• HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase

  2011influential reference
• DDX1, DDX21, and DHX36 helicases form a complex with the adaptor molecule TRIF to sense dsRNA in dendritic cells.

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• Differential utilization of decapping enzymes in mammalian mRNA decay pathways.

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• An RNA Pseudoknot Is Required for Production of Yellow Fever Virus Subgenomic RNA by the Host Nuclease XRN1

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• The human core exosome interacts with differentially localized processive RNases: hDIS3 and hDIS3L

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• Poliovirus-Mediated Disruption of Cytoplasmic Processing Bodies

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• LGP2 is a positive regulator of RIG-I– and MDA5-mediated antiviral responses

  2010cited by this paper
• The crystal structure of Mtr4 reveals a novel arch domain required for rRNA processing

  2010cited by this paper
• Comparison of U2OS and Huh-7 cells for identifying host factors that affect hepatitis C virus RNA replication.

  2010cited by this paper
• Polyadenylation and degradation of incomplete RNA polymerase I transcripts in mammalian cells

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• The many pathways of RNA degradation.

  2009cited by this paper
• Aicardi-Goutieres syndrome and related phenotypes: linking nucleic acid metabolism with autoimmunity.

  2009cited by this paper
• Hepatitis C virus blocks interferon effector function by inducing protein kinase R phosphorylation.

  2009cited by this paper
• Viral evasion of interferon stimulated genes

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• Activation of MDA5 Requires Higher-Order RNA Structures Generated during Virus Infection

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• Distinct Roles of Non-Canonical Poly(A) Polymerases in RNA Metabolism

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• Rift Valley Fever Virus NSs Protein Promotes Post-Transcriptional Downregulation of Protein Kinase PKR and Inhibits eIF2α Phosphorylation

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• The roles of TLRs, RLRs and NLRs in pathogen recognition.

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• Modulation of microRNA processing by p53

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• RIG-I-like antiviral protein in flies

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• Trex1 prevents cell-intrinsic initiation of autoimmunity.

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• Quality control of eukaryotic mRNA: safeguarding cells from abnormal mRNA function.

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• The zinc-finger antiviral protein recruits the RNA processing exosome to degrade the target mRNA

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• P-Body Formation Is a Consequence, Not the Cause, of RNA-Mediated Gene Silencing

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• RNA regulons: coordination of post-transcriptional events

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• Localization of AU-rich Element-containing mRNA in Cytoplasmic Granules Containing Exosome Subunits*

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• Small self-RNA generated by RNase L amplifies antiviral innate immunity

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• Essential function in vivo for Dicer-2 in host defense against RNA viruses in drosophila

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• Reconstitution, activities, and structure of the eukaryotic RNA exosome.

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• RNA-quality control by the exosome

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• The RNA silencing endonuclease Argonaute 2 mediates specific antiviral immunity in Drosophila melanogaster.

  2006cited by this paper
• Initiation of protein synthesis by hepatitis C virus is refractory to reduced eIF2.GTP.Met-tRNA(i)(Met) ternary complex availability.

  2006cited by this paper
• RNA- and Virus-Independent Inhibition of Antiviral Signaling by RNA Helicase LGP2

  2006cited by this paper
• Sindbis Virus Nonstructural Protein nsP2 Is Cytotoxic and Inhibits Cellular Transcription

  2006cited by this paper
• Essential role of mda-5 in type I IFN responses to polyriboinosinic:polyribocytidylic acid and encephalomyocarditis picornavirus.

  2006cited by this paper
• Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses

  2006cited by this paper
• Degradation of RNA in bacteria: comparison of mRNA and stable RNA

  2006cited by this paper
• Shared and Unique Functions of the DExD/H-Box Helicases RIG-I, MDA5, and LGP2 in Antiviral Innate Immunity1

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• The RNA Helicase Lgp2 Inhibits TLR-Independent Sensing of Viral Replication by Retinoic Acid-Inducible Gene-I1

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• Turnip crinkle virus-encoded suppressor of RNA silencing suppresses mRNA decay by interacting with Arabidopsis XRN4.

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• A computational map of the human-SARS-CoV-2 protein–RNA interactome predicted at single-nucleotide resolution

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  2021cites this paper
• RNA stabilization by a poly(A) tail 3′-end binding pocket and other modes of poly(A)-RNA interaction

  2021cites this paper
• Regulation of RNA degradation pathways during the lipopolysaccharide response in Macrophages

  2020cites this paper
• lncRNA Sensing of a Viral Suppressor of RNAi Activates Non-canonical Innate Immune Signaling in Drosophila.

  2020cites this paper
• Regulation of long non-coding RNAs and genome dynamics by the RNA surveillance machinery

  2020cites this paper
• Biochemical Characterization of Yeast Xrn1.

  2020cites this paper
• Monkeypox virus emergence in wild chimpanzees reveals distinct clinical outcomes and viral diversity

  2020cites this paper
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  2020cites this paper
• Nucleic acid-mediated PAMP-triggered immunity in plants.

  2020cites this paper
• Viral silencing suppressors and cellular proteins partner with plant RRP6-like exoribonucleases

  2020cites this paper
• Immune Sensing Mechanisms that Discriminate Self from Altered Self and Foreign Nucleic Acids

  2020cites this paper
• Roadblocks and fast tracks: How RNA binding proteins affect the viral RNA journey in the cell

  2020cites this paper
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  2020cites this paper
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  2020cites this paper
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  2020cites this paper
• RNA helicases are hubs that orchestrate exosome-dependent 3'-5' decay.

  2020cites this paper
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  2020cites this paper
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  2019cites this paper
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  2019cites this paper
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  2019cites this paper
• Seasonal Variability and Shared Molecular Signatures of Inactivated Influenza Vaccination in Young and Older Adults

  2019cites this paper
• SnapShot: The RNA Exosome.

  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2017cites this paper
• Identification of phlebovirus and arenavirus RNA sequences that stall and repress the exoribonuclease XRN1

  2017cites this paper
• Influenza A Virus–Host Protein Interactions Control Viral Pathogenesis

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