MicroRNA in Control of Gene Expression: An Overview of Nuclear Functions

Catalanotto, Caterina; Cogoni, Carlo; Zardo, Giuseppe

doi:10.3390/ijms17101712

Cited by 982 publications

(766 citation statements)

References 117 publications

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“…MicroRNAs are evolutionarily conserved, small (~22 nucleotide long) non-coding RNAs, involved in transcriptional and posttranscriptional regulation of biological processes (69). Recently, it has been shown that EVs are rich sources of miRNAs, since, being packed in membrane-coated vesicles, they are more protected from RNAses than in a naked form (70, 71).…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles Mediate Radiation-Induced Systemic Bystander Signals in the Bone Marrow and Spleen

et al. 2017

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Radiation-induced bystander effects refer to the induction of biological changes in cells not directly hit by radiation implying that the number of cells affected by radiation is larger than the actual number of irradiated cells. Recent in vitro studies suggest the role of extracellular vesicles (EVs) in mediating radiation-induced bystander signals, but in vivo investigations are still lacking. Here, we report an in vivo study investigating the role of EVs in mediating radiation effects. C57BL/6 mice were total-body irradiated with X-rays (0.1, 0.25, 2 Gy), and 24 h later, EVs were isolated from the bone marrow (BM) and were intravenously injected into unirradiated (so-called bystander) animals. EV-induced systemic effects were compared to radiation effects in the directly irradiated animals. Similar to direct radiation, EVs from irradiated mice induced complex DNA damage in EV-recipient animals, manifested in an increased level of chromosomal aberrations and the activation of the DNA damage response. However, while DNA damage after direct irradiation increased with the dose, EV-induced effects peaked at lower doses. A significantly reduced hematopoietic stem cell pool in the BM as well as CD4+ and CD8+ lymphocyte pool in the spleen was detected in mice injected with EVs isolated from animals irradiated with 2 Gy. These EV-induced alterations were comparable to changes present in the directly irradiated mice. The pool of TLR4-expressing dendritic cells was different in the directly irradiated mice, where it increased after 2 Gy and in the EV-recipient animals, where it strongly decreased in a dose-independent manner. A panel of eight differentially expressed microRNAs (miRNA) was identified in the EVs originating from both low- and high-dose-irradiated mice, with a predicted involvement in pathways related to DNA damage repair, hematopoietic, and immune system regulation, suggesting a direct involvement of these pathways in mediating radiation-induced systemic effects. In conclusion, we proved the role of EVs in transmitting certain radiation effects, identified miRNAs carried by EVs potentially responsible for these effects, and showed that the pattern of changes was often different in the directly irradiated and EV-recipient bystander mice, suggesting different mechanisms.

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Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles Mediate Radiation-Induced Systemic Bystander Signals in the Bone Marrow and Spleen

et al. 2017

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“…They act by inhibiting gene expression or by promoting gene degradation [131]. It is estimated that miRNAs regulate between 30 and 90% of genes in the genome, as a single miRNA may regulate hundreds of genes [132, 133].…”

Section: Mechanisms Of Innate Immune Activation In Ssmentioning

confidence: 99%

Innate immunity in Sjögren's syndrome

Kiripolsky

McCabe

Kramer

2017

Clinical Immunology

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Sjögren’s syndrome (SS) is an autoimmune disease of exocrine tissue that primarily affects women. Although patients typically experience xerostomia and xerophthalmia, numerous systemic disease manifestations are seen. Innate immune hyperactivity is integral to many autoimmune diseases, including SS. Results from SS mouse models suggest that innate immune dysregulation drives disease and this is a seminal event in SS pathogenesis. Findings in SS patients corroborate those in mouse models, as innate immune cells and pathways are dysregulated both in exocrine tissue and in peripheral blood. We will review the role of the innate immune system in SS pathogenesis. We will discuss the etiology of SS with an emphasis on innate immune dysfunction. Moreover, we will review the innate cells that mediate inflammation in SS, the pathways implicated in disease, and the potential mechanisms governing their dysregulation. Finally, we will discuss emerging therapeutic approaches to target dysregulated innate immune signaling in SS.

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“…[21][22][23][24] They are single stranded and approximately 17-24 bases long. Aberrant miR activity has been associated with a number of neurodegenerative diseases including PD.…”

Section: Introductionmentioning

confidence: 99%

Loss of MicroRNA-7 Regulation Leads to α-Synuclein Accumulation and Dopaminergic Neuronal Loss In Vivo

et al. 2017

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General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/pure/about/ebr-terms show that miR-7 is decreased in the substantia nigra of patients with PD and therefore may play an essential role in the regulation of α-synuclein expression. Furthermore, we have found that lentiviral mediated expression of miR-7 complementary binding sites to stably induce a loss of miR-7 function results in an increase in α-synuclein expression in vitro and in vivo. We have also shown that depletion of miR-7 using a miR-decoy produces a loss of nigral dopaminergic neurons accompanied by a reduction of striatal dopamine content. These data suggest that miR-7 has an important role in the regulation of α-synuclein and dopamine physiology and may provide a new paradigm to study the pathology of PD.3

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MicroRNA in Control of Gene Expression: An Overview of Nuclear Functions

Cited by 982 publications

References 117 publications

Extracellular Vesicles Mediate Radiation-Induced Systemic Bystander Signals in the Bone Marrow and Spleen

Extracellular Vesicles Mediate Radiation-Induced Systemic Bystander Signals in the Bone Marrow and Spleen

Innate immunity in Sjögren's syndrome

Loss of MicroRNA-7 Regulation Leads to α-Synuclein Accumulation and Dopaminergic Neuronal Loss In Vivo

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