Small RNAs, Big Diseases

Rzeszutek, Iwona; Singh, Aditi

doi:10.3390/ijms21165699

Cited by 10 publications

(6 citation statements)

References 288 publications

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“…These include endoplasmic reticulum, ribosomes, tRNAs, and other cytosolic factors but also regulatory molecules such as transcription factors and microRNAs (miRNA). Canonical gene expression regulation by miRNAs is based on their binding to complementary sequences on RNA targets, requiring a perfect match with the 2–8 nucleotides of the miRNA 5′ region (seed region); then, miRNAs mediate translational repression and/or degradation of the RNA targets ( Rzeszutek and Singh, 2020 ). As posttranscriptional regulators, miRNAs play an important role in a broad array of cellular functions, including the complex molecular interplay that is established upon viral infection of host cells ( Umbach and Cullen, 2009 ; Trobaugh and Klimstra, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Human MicroRNAs Interacting With SARS-CoV-2 RNA Sequences: Computational Analysis and Experimental Target Validation

2021

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel RNA virus affecting humans, causing a form of acute pulmonary respiratory disorder named COVID-19, declared a pandemic by the World Health Organization. MicroRNAs (miRNA) play an emerging and important role in the interplay between viruses and host cells. Although the impact of host miRNAs on SARS-CoV-2 infection has been predicted, experimental data are still missing. This study started by a bioinformatics prediction of cellular miRNAs potentially targeting viral RNAs; then, a number of criteria also based on experimental evidence and virus biology were applied, giving rise to eight promising binding miRNAs. Their interaction with viral sequences was experimentally validated by transfecting luciferase-based reporter plasmids carrying viral target sequences or their inverted sequences into the lung A549 cell line. Transfection of the reporter plasmids resulted in a reduction of luciferase activity for five out of the eight potential binding sites, suggesting responsiveness to endogenously expressed miRNAs. Co-transfection of the reporter plasmids along with miRNA mimics led to a further and strong reduction of luciferase activity, validating the interaction between miR-219a-2-3p, miR-30c-5p, miR-378d, miR-29a-3p, miR-15b-5p, and viral sequences. miR-15b was also able to repress plasmid-driven Spike expression. Intriguingly, the viral target sequences are fully conserved in more recent variants such as United Kingdom variant B.1.1.7 and South Africa 501Y.V2. Overall, this study provides a first experimental evidence of the interaction between specific cellular miRNAs and SARS-CoV-2 sequences, thus contributing to understanding the molecular mechanisms underlying virus infection and pathogenesis to envisage innovative therapeutic interventions and diagnostic tools.

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Section: Introductionmentioning

confidence: 99%

Human MicroRNAs Interacting With SARS-CoV-2 RNA Sequences: Computational Analysis and Experimental Target Validation

2021

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“…The RNAi machinery is also associated with various pathological states [44][45][46] . Specifically, it was found to contribute to the aberrant activation of pathogenic RNA toxicity mechanisms in nematodes 47 , drosophila 48 , and mammals [49][50][51] .…”

Section: Introductionmentioning

confidence: 99%

RNA interference mediates RNA toxicity with parent-of-origin effects inC. elegansexpressing CTG repeats

Braun

Shoshani

Teixeira

et al. 2021

Preprint

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Nucleotide repeat expansions are a hallmark of over 40 neurodegenerative diseases. These repeats cause RNA toxicity and trigger multisystemic symptoms that worsen with age. RNA toxicity can trigger, through an unclear mechanism, severe disease manifestation in infants that inherited repeats from their mothers. Here we show in Caenorhabditis elegans how RNA interference machinery causes intergenerational toxicity through inheritance of siRNAs derived from CUG repeats. The maternal repeat-derived small RNAs cause transcriptomic changes in the offspring, reduce motility and shorten lifespan. However, the toxicity phenotypes in the offspring can be rescued by perturbing the RNAi machinery in affected mothers. This points to a novel mechanism linking maternal bias and the RNAi machinery and suggests that toxic RNA is transmitted to offspring and causes disease phenotypes through intergenerational epigenetic inheritance.

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“…Since the discovery of the relationship between miRNA deregulation and CLL [ 16 ], many research groups have focused their attention to investigation of the connection between miRNA and various cancers (reviewed by [ 24 ]).…”

Section: Lung Cancer and Mirnamentioning

confidence: 99%

The Impact of Air Pollution Exposure on the MicroRNA Machinery and Lung Cancer Development

Šíma

Rössnerová

Simova

et al. 2021

JPM

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Small non-coding RNA molecules (miRNAs) play an important role in the epigenetic regulation of gene expression. As these molecules have been repeatedly implicated in human cancers, they have been suggested as biomarkers of the disease. Additionally, miRNA levels have been shown to be affected by environmental pollutants, including airborne contaminants. In this review, we searched the current literature for miRNAs involved in lung cancer, as well as miRNAs deregulated as a result of exposure to air pollutants. We then performed a synthesis of the data and identified those molecules commonly deregulated under both conditions. We detected a total of 25 miRNAs meeting the criteria, among them, miR-222, miR-21, miR-126-3p, miR-155 and miR-425 being the most prominent. We propose these miRNAs as biomarkers of choice for the identification of human populations exposed to air pollution with a significant risk of developing lung cancer.

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Small RNAs, Big Diseases

Cited by 10 publications

References 288 publications

Human MicroRNAs Interacting With SARS-CoV-2 RNA Sequences: Computational Analysis and Experimental Target Validation

Human MicroRNAs Interacting With SARS-CoV-2 RNA Sequences: Computational Analysis and Experimental Target Validation

RNA interference mediates RNA toxicity with parent-of-origin effects inC. elegansexpressing CTG repeats

The Impact of Air Pollution Exposure on the MicroRNA Machinery and Lung Cancer Development

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