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RNA Biology Apr 2017
Topics: Animals; Host-Pathogen Interactions; Humans; MicroRNAs; Plants; RNA Interference
PubMed: 28296620
DOI: 10.1080/15476286.2017.1306172 -
Viruses Feb 2022Multiple antiviral immunities were developed to defend against viral infection in hosts. RNA interference (RNAi)-based antiviral innate immunity is evolutionarily... (Review)
Review
Multiple antiviral immunities were developed to defend against viral infection in hosts. RNA interference (RNAi)-based antiviral innate immunity is evolutionarily conserved in eukaryotes and plays a vital role against all types of viruses. During the arms race between the host and virus, many viruses evolve viral suppressors of RNA silencing (VSRs) to inhibit antiviral innate immunity. Here, we reviewed the mechanism at different stages in RNAi-based antiviral innate immunity in plants and the counteractions of various VSRs, mainly upon infection of RNA viruses in model plant Arabidopsis. Some critical challenges in the field were also proposed, and we think that further elucidating conserved antiviral innate immunity may convey a broad spectrum of antiviral strategies to prevent viral diseases in the future.
Topics: Arabidopsis; Host-Pathogen Interactions; Immunity, Innate; Plant Diseases; Plant Immunity; RNA Interference; RNA Virus Infections
PubMed: 35216025
DOI: 10.3390/v14020432 -
Nature Cell Biology Dec 2022The endoplasmic reticulum (ER) coordinates mRNA translation and processing of secreted and endomembrane proteins. ER-associated degradation (ERAD) prevents the...
The endoplasmic reticulum (ER) coordinates mRNA translation and processing of secreted and endomembrane proteins. ER-associated degradation (ERAD) prevents the accumulation of misfolded proteins in the ER, but the physiological regulation of this process remains poorly characterized. Here, in a genetic screen using an ERAD model substrate in Caenorhabditis elegans, we identified an anti-viral RNA interference pathway, referred to as ER-associated RNA silencing (ERAS), which acts together with ERAD to preserve ER homeostasis and function. Induced by ER stress, ERAS is mediated by the Argonaute protein RDE-1/AGO2, is conserved in mammals and promotes ER-associated RNA turnover. ERAS and ERAD are complementary, as simultaneous inactivation of both quality-control pathways leads to increased ER stress, reduced protein quality control and impaired intestinal integrity. Collectively, our findings indicate that ER homeostasis and organismal health are protected by synergistic functions of ERAS and ERAD.
Topics: RNA Interference; Endoplasmic Reticulum
PubMed: 36471127
DOI: 10.1038/s41556-022-01025-4 -
International Journal of Molecular... Dec 2022MicroRNAs (miRNAs) act as master regulators of gene expression in homeostasis and disease. Despite the rapidly growing body of evidence on the theranostic potential of... (Review)
Review
MicroRNAs (miRNAs) act as master regulators of gene expression in homeostasis and disease. Despite the rapidly growing body of evidence on the theranostic potential of restoring miRNA levels in pre-clinical models, the translation into clinics remains limited. Here, we review the current knowledge of miRNAs as T-cell targeting immunotherapeutic tools, and we offer an overview of the recent advances in miRNA delivery strategies, clinical trials and future perspectives in RNA interference technologies.
Topics: MicroRNAs; T-Lymphocytes; RNA Interference; Precision Medicine; Immunotherapy
PubMed: 36613706
DOI: 10.3390/ijms24010250 -
Current Opinion in Immunology Oct 2018Infection of plants and insects with RNA and DNA viruses triggers Dicer-dependent production of virus-derived small interfering RNAs (vsiRNAs), which subsequently guide... (Review)
Review
Infection of plants and insects with RNA and DNA viruses triggers Dicer-dependent production of virus-derived small interfering RNAs (vsiRNAs), which subsequently guide specific virus clearance by RNA interference (RNAi). Consistent with a major antiviral function of RNAi, productive virus infection in these eukaryotic hosts depends on the expression of virus-encoded suppressors of RNAi (VSRs). The eukaryotic RNAi pathway is highly conserved, particularly between insects and mammals. This review will discuss key recent findings that indicate a natural antiviral function of the RNAi pathway in mammalian cells. We will summarize the properties of the characterized mammalian vsiRNAs and VSRs and highlight important questions remaining to be addressed on the function and mechanism of mammalian antiviral RNAi.
Topics: Animals; Humans; Mammals; Protective Agents; RNA Interference; RNA, Viral; Virus Diseases; Viruses
PubMed: 30015086
DOI: 10.1016/j.coi.2018.06.010 -
International Journal of Molecular... Jun 2023Antisense RNA was observed to elicit plant disease resistance and post-translational gene silencing (PTGS). The universal mechanism of RNA interference (RNAi) was shown... (Review)
Review
Antisense RNA was observed to elicit plant disease resistance and post-translational gene silencing (PTGS). The universal mechanism of RNA interference (RNAi) was shown to be induced by double-stranded RNA (dsRNA), an intermediate produced during virus replication. Plant viruses with a single-stranded positive-sense RNA genome have been instrumental in the discovery and characterization of systemic RNA silencing and suppression. An increasing number of applications for RNA silencing have emerged involving the exogenous application of dsRNA through spray-induced gene silencing (SIGS) that provides specificity and environmentally friendly options for crop protection and improvement.
Topics: RNA Interference; Gene Silencing; RNA, Double-Stranded; RNA, Small Interfering; Plants; Plant Diseases
PubMed: 37298705
DOI: 10.3390/ijms24119755 -
Annual Review of Virology Sep 2021Viroids are small, single-stranded, circular RNAs infecting plants. Composed of only a few hundred nucleotides and being unable to code for proteins, viroids represent... (Review)
Review
Viroids are small, single-stranded, circular RNAs infecting plants. Composed of only a few hundred nucleotides and being unable to code for proteins, viroids represent the lowest level of complexity for an infectious agent, even below that of the smallest known viruses. Despite the relatively small size, viroids contain RNA structural elements embracing all the information needed to interact with host factors involved in their infectious cycle, thus providing models for studying structure-function relationships of RNA. Viroids are specifically targeted to nuclei (family ) or chloroplasts (family ), where replication based on rolling-circle mechanisms takes place. They move locally and systemically through plasmodesmata and phloem, respectively, and may elicit symptoms in the infected host, with pathogenic pathways linked to RNA silencing and other plant defense responses. In this review, recent advances in the dissection of the complex interplay between viroids and plants are presented, highlighting knowledge gaps and perspectives for future research.
Topics: Plant Diseases; Plants; RNA Interference; RNA, Viral; Viroids
PubMed: 34255541
DOI: 10.1146/annurev-virology-091919-092331 -
Genes & Development Feb 2018Adenosine deaminases that act on RNA (ADARs) convert adenosines (A) to inosines (I) in stretches of dsRNA. The biological purpose of these editing events for the vast... (Review)
Review
Adenosine deaminases that act on RNA (ADARs) convert adenosines (A) to inosines (I) in stretches of dsRNA. The biological purpose of these editing events for the vast majority of ADAR substrates is largely unknown. In this issue of Reich and colleagues (pp. 271-282) demonstrate that in , A-to-I editing in double-stranded regions of protein-coding transcripts protects these RNAs from targeting by the RNAi pathway. Disruption of this safeguard through loss of ADAR activity coupled with enhanced RNAi results in developmental abnormalities and profound changes in gene expression that suggest aberrant induction of an antiviral response. Thus, editing of cellular dsRNA by ADAR helps prevent host RNA silencing and inadvertent antiviral activity.
Topics: Animals; Antiviral Agents; Caenorhabditis elegans; RNA Editing; RNA Interference; RNA, Double-Stranded; Radar
PubMed: 29491134
DOI: 10.1101/gad.313049.118 -
The Plant Cell Aug 2022Host-induced gene silencing (HIGS) refers to the silencing of genes in pathogens and pests by expressing homologous double-stranded RNAs (dsRNA) or artificial microRNAs... (Review)
Review
Host-induced gene silencing (HIGS) refers to the silencing of genes in pathogens and pests by expressing homologous double-stranded RNAs (dsRNA) or artificial microRNAs (amiRNAs) in the host plant. The discovery of such trans-kingdom RNA silencing has enabled the development of RNA interference-based approaches for controlling diverse crop pathogens and pests. Although HIGS is a promising strategy, the mechanisms by which these regulatory RNAs translocate from plants to pathogens, and how they induce gene silencing in pathogens, are poorly understood. This lack of understanding has led to large variability in the efficacy of various HIGS treatments. This variability is likely due to multiple factors, such as the ability of the target pathogen or pest to take up and/or process RNA from the host, the specific genes and target sequences selected in the pathogen or pest for silencing, and where, when, and how the dsRNAs or amiRNAs are produced and translocated. In this review, we summarize what is currently known about the molecular mechanisms underlying HIGS, identify key unanswered questions, and explore strategies for improving the efficacy and reproducibility of HIGS treatments in the control of crop diseases.
Topics: Gene Silencing; Plant Diseases; Plants; RNA Interference; RNA, Double-Stranded; Reproducibility of Results
PubMed: 35666177
DOI: 10.1093/plcell/koac165 -
Virus Research Aug 2018Zika virus (ZIKV; family Flaviviridae; genus Flavivirus) is a pathogenic mosquito-borne RNA virus that currently threatens human health in the Americas, large parts of... (Review)
Review
Zika virus (ZIKV; family Flaviviridae; genus Flavivirus) is a pathogenic mosquito-borne RNA virus that currently threatens human health in the Americas, large parts of Asia and occasionally elsewhere in the world. ZIKV infection is often asymptomatic but can cause severe symptoms including congenital microcephaly and Guillain-Barré syndrome. The positive single-stranded RNA genome of the mosquito-borne ZIKV requires effective replication in two evolutionary distinct hosts - mosquitoes and primates. In addition to some of the viral proteins, the ZIKV genomic RNA and functional RNAs produced thereof aid in the establishment of productive infection and the evasion of host cell antiviral responses. ZIKV has evolved to contain a nucleotide composition and RNA modifications, such as methylation and the formation of G-quadruplexes that allow effective replication in both hosts. Furthermore, a number of host factors interact with the viral genome to modulate RNA replication. Importantly, the ZIKV genome produces non-coding subgenomic flavivirus RNA (sfRNA) due to stalling of host 5'- 3' ribonucleases on viral RNA structures in the 3' untranslated region (UTR). This sfRNA (sfRNA) exerts important proviral functions such as antagonizing the innate interferon response and RNA interference. Here, we discuss the ZIKV genomic RNA and functional RNAs thereof to assess their significance during ZIKV infection. Understanding the details of the ZIKV infection cycle will aid in the development of effective antiviral strategies and safe vaccines.
Topics: Animals; Host-Pathogen Interactions; Humans; Methylation; RNA Interference; RNA, Untranslated; RNA, Viral; Virus Replication; Zika Virus; Zika Virus Infection
PubMed: 28864425
DOI: 10.1016/j.virusres.2017.08.015