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

Molleston, Jerome M.; Sabin, Leah R.; Moy, Ryan H.; Menghani, Sanjay V.; Rausch, Keiko; Gordesky-Gold, Beth; Hopkins, Kaycie C.; Zhou, Rui; Jensen, Torben Heick; Wilusz, Jeremy E.; Cherry, Sara

doi:10.1101/gad.284604.116

Cited by 54 publications

(46 citation statements)

References 84 publications

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“…The Trf-Air-Mtr4 polyadenylation (TRAMP) complex is a set of cofactors that prepares RNA substrates for degradation by the nuclear RNA exosome (see below; Table 1; LaCava et al 2005;Wyers et al 2005); however, this complex was recently shown to participate in viral defense in the cytoplasm (Molleston et al 2016). Infection of human and Drosophila cells with the disparate RNA viruses vesicular stomatitis virus, Sindbis virus, or Rift Valley fever virus (RVFV) was potentiated by knockdown of exosome and TRAMP components.…”

Section: Viral Defensementioning

confidence: 99%

Targeting RNA for processing or destruction by the eukaryotic RNA exosome and its cofactors

2017

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The eukaryotic RNA exosome is an essential and conserved protein complex that can degrade or process RNA substrates in the 3 ′ -to-5 ′ direction. Since its discovery nearly two decades ago, studies have focused on determining how the exosome, along with associated cofactors, achieves the demanding task of targeting particular RNAs for degradation and/or processing in both the nucleus and cytoplasm. In this review, we highlight recent advances that have illuminated roles for the RNA exosome and its cofactors in specific biological pathways, alongside studies that attempted to dissect these activities through structural and biochemical characterization of nuclear and cytoplasmic RNA exosome complexes.

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Section: Viral Defensementioning

confidence: 99%

Targeting RNA for processing or destruction by the eukaryotic RNA exosome and its cofactors

2017

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“…The Drosophila-specific pathogen DCV was also often included in the screens because it could serve as a model for pathogenic enterovirus infections in mammals [110], while other Drosophila-(Nora virus) or insect-specific viruses (FHV) were rarely included. Besides genome-wide screens, also targeted screens were performed, for instance targeting specific signaling pathways, immune genes, RNA helicases, RNA metabolism and endoplasmic reticulum (ER)-associated proteins [99,[111][112][113][114].…”

Section: Identification Of Host Factors That Restrict Viral Infectionmentioning

confidence: 99%

“…Furthermore, it was regularly observed that host factors in Drosophila cells were conserved in mammalian (human) cells [112][113][114][117][118][119][120]. The results of the screens with respect to the (validated) identification of both new resistance mechanisms (VRFs, "antiviral genes") as well as (often virus-specific) cellular processes that are limiting to viral infection (VSFs, "proviral genes") are summarized in Table 1.…”

Section: Identification Of Host Factors That Restrict Viral Infectionmentioning

confidence: 99%

“…An antiviral role was also demonstrated for the enzyme aldolase, for which the nuclear transport of its mRNA was shown to be dependent on dXPO1. It is not surprising that also the (non-RNAi) RNA degradation machinery was identified as an antiviral defense mechanism acting against arboviruses with both positive (SINV) and negative strand (VSV, RVFV) ssRNA genomes [113]. Viral RNAs often have distinctive features such as dsRNA structures, 5'-triphosphates and short or absent poly(A) tails and such "aberrant" RNAs can be bound by RNA-binding cofactor complexes for subsequent targeting to the RNA degradation machinery.…”

Section: Broad Range Antiviral Defense Programsmentioning

confidence: 99%

“…Viral RNAs often have distinctive features such as dsRNA structures, 5'-triphosphates and short or absent poly(A) tails and such "aberrant" RNAs can be bound by RNA-binding cofactor complexes for subsequent targeting to the RNA degradation machinery. In targeted RNAi screens both the 3'-to-5' RNA exosome and components of the exosome cofactor complex TRAMP (Trf4/5-Air1/2-Mtr4 polyadenylation) were implicated in antiviral defense (Table 1; [113]). On the other hand, no factors of the other exosome cofactor complexes (Ski, NEXT) were found to be involved, revealing some specificity in the viral RNA recognition process.…”

Section: Broad Range Antiviral Defense Programsmentioning

confidence: 99%

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Defense Mechanisms against Viral Infection in <em>Drosophila</em>: RNAi versus Non-RNAi

Swevers¹,

Liu²,

Smagghe³

2018

Preprint

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RNAi is considered a major antiviral defense mechanism in insects but its relative importance compared to other antiviral pathways has not been evaluated comprehensively. Here, it is attempted to give an overview of the antiviral defense mechanisms in Drosophila that involve both RNAi and non-RNAi to acquire a sense of their relative importance. While RNAi is considered important in most viral infections, many other pathways can exist that confer antiviral resistance. It is noted that very few direct recognition mechanisms of virus infections have been identified in Drosophila and that the activation of immune pathways may be accomplished indirectly through cell damage incurred by viral replication. In several cases, protection against viral infection can be obtained in RNAi mutants by non-RNAi mechanisms, confirming the variability of the RNAi defense mechanism according to the type of infection and the physiological status of the host. This analysis invites to investigate more systematically the relative contribution of RNAi in the antiviral response and more specifically to ask whether RNAi efficiency is affected when other defense mechanisms predominate. While Drosophila can function as a useful model, this issue may be more critical for economically important insects that are either controlled (agricultural pests and vectors of diseases) or protected from parasite infection (beneficial insects as bees) by RNAi products.

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Regulation of cytoplasmic RNA stability: Lessons from Drosophila

Towler

Newbury

2018

WIREs RNA

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The process of RNA degradation is a critical level of regulation contributing to the control of gene expression. In the last two decades a number of studies have shown the specific and targeted nature of RNA decay and its importance in maintaining homeostasis. The key players within the pathways of RNA decay are well conserved with their mutation or disruption resulting in distinct phenotypes as well as human disease. Model organisms including Drosophila melanogaster have played a substantial role in elucidating the mechanisms conferring control over RNA stability. A particular advantage of this model organism is that the functions of ribonucleases can be assessed in the context of natural cells within tissues in addition to individual immortalized cells in culture. Drosophila RNA stability research has demonstrated how the cytoplasmic decay machines, such as the exosome, Dis3L2 and Xrn1, are responsible for regulating specific processes including apoptosis, proliferation, wound healing and fertility. The work discussed here has begun to identify specific mRNA transcripts that appear sensitive to specific decay pathways representing mechanisms through which the ribonucleases control mRNA stability. Drosophila research has also contributed to our knowledge of how specific RNAs are targeted to the ribonucleases including AU rich elements, miRNA targeting and 3' tailing. Increased understanding of these mechanisms is critical to elucidating the control elicited by the cytoplasmic ribonucleases which is relevant to human disease. This article is categorized under: RNA in Disease and Development > RNA in Development RNA Turnover and Surveillance > Regulation of RNA Stability RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms.

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

Cited by 54 publications

References 84 publications

Targeting RNA for processing or destruction by the eukaryotic RNA exosome and its cofactors

Targeting RNA for processing or destruction by the eukaryotic RNA exosome and its cofactors

Defense Mechanisms against Viral Infection in <em>Drosophila</em>: RNAi versus Non-RNAi

Regulation of cytoplasmic RNA stability: Lessons from Drosophila

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