The Challenges of Long-Term Transcriptional Gene Silencing by RNA Viruses

Ma, Xiaoxia; Ma, Zhiyong; Pan, Qiuwei

doi:10.1016/j.tibs.2018.06.010

Cited by 4 publications

(3 citation statements)

References 11 publications

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“…Recently, it has been discovered that some picornaviruses only cause an acute and self-limiting infection without major pathogenesis in hosts requiring more research on therapeutic approach (Weinberg and Morris, 2016; Ma et al, 2018b). The role of non-structural proteins in such picornaviruses may make contributions to better understand not only the therapeutic antiviral activity of IFNs, but also may reveal how these proteins (with or without protease activities) influence and control the IFN signaling transduction in vivo .…”

Section: Discussionmentioning

confidence: 99%

The Strategy of Picornavirus Evading Host Antiviral Responses: Non-structural Proteins Suppress the Production of IFNs

Stipkovits²,

Szathmáry³

et al. 2018

Front. Microbiol.

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Viral infections trigger the innate immune system to produce interferons (IFNs), which play important role in host antiviral responses. Co-evolution of viruses with their hosts has favored development of various strategies to evade the effects of IFNs, enabling viruses to survive inside host cells. One such strategy involves inhibition of IFN signaling pathways by non-structural proteins. In this review, we provide a brief overview of host signaling pathways inducing IFN production and their suppression by picornavirus non-structural proteins. Using this strategy, picornaviruses can evade the host immune response and replicate inside host cells.

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Section: Discussionmentioning

confidence: 99%

The Strategy of Picornavirus Evading Host Antiviral Responses: Non-structural Proteins Suppress the Production of IFNs

Stipkovits²,

Szathmáry³

et al. 2018

Front. Microbiol.

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“…According to tRNA copy numbers for the tRNA abundance pool in CHO cell line (Genomic tRNA Database), when the position +4 mutates different nucleotide types in bicistronic reporter plasmids, the tRNA abundances for the second codon (+4XTG+6, X means any nucleotide, tRNA copy number for GTG is 9, tRNA copy number for CTG is 10, tRNA copy number for TTG is 4, tRNA copy number for ATG is 16) following the start codon have no obvious effect on mediating the EGFP gene expression levels. This result implies that nucleotide context at +4 nucleotide position might influence the local structural formation rather than tRNA abundances, leading to the changes of gene expression mediated by HCV IRES (Jaafar et al, 2016;Bugaud et al, 2017;Ma et al, 2018;Mengardi et al, 2017;Ross et al, 2017;Zhu et al, 2017). Of note, the results show that the positions -3A and +4G had a better performance in improving the translation efficiency mediated by HCV IRES than the preferred nucleotide usage bias (-3A, +4A) in the positions -3 & +4 of the translation initiation region of HCV, implying that the Kozak-like nucleotide context (-3A, +4G) probably impacts the ribosome binding to the translation initiation region of HCV.…”

Section: Discussionmentioning

confidence: 99%

The effects of nucleotide usage in key nucleotide positions +4 and -3 flanking start codon on translation levels mediated by IRES of hepatitis C virus

Ma¹,

Ma²,

Chang³

et al. 2018

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Internal ribosomal entry site (IRES) functions as a cis-acting RNA element, which drives an alternative and cap-independent translation initiation pathway. Currently, there are few studies on effects of nucleotide usages at key nucleotide positions +4 and-3 flanking start codon mediated by IRES of hepatitis C virus (HCV). Herein, we focus on the effect of nucleotide usages at-3 and +4 positions mediated by HCV IRES. The nucleotide contexts flanking AUG start codon employed by HCV IRES is firstly analyzed. We found that each position in the six nucleotide positions (-4 to +6) flanking start codon of HCV has a strong tendency to select the specific nucleotide. A set of bicistronic expression vectors containing CAT gene, HCV IRES and EGFP gene were constructed, including 16 different nucleotide combinations at position-3 and +4. Each set, in which nucleotide at the-3 and +4 position has been changed into different nucleotides, included 16 types of bicistronic expression vectors. It was found that the purine nucleotide at the position-3 or +4 obviously impacts on HCV IRES-related expression, and IRES-driven translation is potentially influenced by the Kozak rule. Our results suggest that optimization of nucleotides at positions-3 and +4 is a convenient and efficient way to enhance the level of IRES-mediated translation.

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“…Yao et al (2019) reported that exogenous delivery of miR-124 suppresses the expression of p38 and p62 and attenuates microglia activation in the substantia nigra pars compacta of MPTP-treated mice. However, the disadvantages of viral vectors (such as the immunogenicity/inflammatory response and low loading capacity) limit their application in gene delivery and make it difficult to achieve large-scale manufacturing and quality control (Itaka and Kataoka, 2009;Ma et al, 2018;Pfister et al, 2018). Compared with viral vectors, non-viral vector delivery systems (liposomes, polymer-based systems, and inorganic nanoparticles) are diverse and relatively safe and can effectively avoid the problems faced by viral vectors through reasonable design and appropriate modification.…”

Section: Mir-124-based Therapeutic Strategies and Mir Deliverymentioning

confidence: 99%

MiR-124 and the Underlying Therapeutic Promise of Neurodegenerative Disorders

et al. 2020

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Neurodegenerative disorders (NDDs) are a group of chronic progressive neurological diseases based on primary neurodegeneration. The common pathological characteristics of various NDDs are neuronal degeneration, deletion, glial cell proliferation, and hypertrophy at specific locations in the nervous system. Proliferation and hypertrophy of microglia are manifestations of inflammation. MicroRNAs (miRNAs) have emerged as pivotal regulators of glial cells. MiRNAs are small non-coding molecules that regulate gene expression. Altered expression of miRNAs has been associated with several NDD pathological processes, among which regulation of the inflammatory response is key and a research hotspot at present. At the same time, miRNAs are also biological markers for diagnosis and potential targets for treating NDDs. MiR-124 is highly conserved and enriched in the mammalian brain. Emerging studies have suggested that miR-124 is closely related to the pathogenesis of NDDs and may be an effective treatment strategy to reduce inflammation associated with NDDs. In this review, we describe a summary of general miRNA biology, implications in pathophysiology, the potential roles of miR-124 associated with inflammation, and the use of miRNA as a future biomarker and an application for NDD therapy.

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The Challenges of Long-Term Transcriptional Gene Silencing by RNA Viruses

Cited by 4 publications

References 11 publications

The Strategy of Picornavirus Evading Host Antiviral Responses: Non-structural Proteins Suppress the Production of IFNs

The Strategy of Picornavirus Evading Host Antiviral Responses: Non-structural Proteins Suppress the Production of IFNs

The effects of nucleotide usage in key nucleotide positions +4 and -3 flanking start codon on translation levels mediated by IRES of hepatitis C virus

MiR-124 and the Underlying Therapeutic Promise of Neurodegenerative Disorders

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