Noncoding RNA Regulation of Dopamine Signaling in Diseases of the Central Nervous System

Carrick, William T.; Burks, Brandi; Cairns, Murray J.; Kocerha, Jannet

doi:10.3389/fmolb.2016.00069

Cited by 15 publications

(3 citation statements)

References 75 publications

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“…For example, Ago2, not 1, 3, and 4, is downregulated in brain lysates from encephalomyelitis mice, the expression level of several miR-NAs, including let-7a-5p, let-7e-5p, let-7f-5p, 106b-5p, 144-3p, and 188a-5p, display a significant reduction (Lewkowicz et al, 2015), suggesting that Ago2 is involved in the etiology of CNS diseases (Savas et al, 2008). Deficiency of Ago2 in D2R neurons relieves self-administration of cocaine due to the declined content of miRNAs in the mouse striatum (Schaefer et al, 2010), revealing a vital role of Ago2 in the treatment of CNS diseases (Carrick et al, 2016). Here, we found that nociceptive behavior caused the decrease of spinal Ago2 level, and overexpressing Ago2 significantly attenuated the pain hypersensitivity.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-1224 Splicing CircularRNA-Filip1l in an Ago2-Dependent Manner Regulates Chronic Inflammatory Pain via Targeting Ubr5

Pan

Sun

et al. 2019

J. Neurosci.

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Dysfunctions of gene transcription and translation inthe nociceptive pathways play the critical role in development and maintenance of chronic pain. Circular RNAs (circRNAs) are emerging as new players in regulation of gene expression, but whether and how circRNAs are involved in chronic pain remain elusive. We showed here that complete Freund's adjuvant-induced chronic inflammation pain significantly increased circRNA-Filip1l (filamin A interacting protein 1-like) expression in spinal neurons of mice. Blockage of this increase attenuated complete Freund's adjuvant-induced nociceptive behaviors, and overexpression of spinal circRNA-Filip1l in naive mice mimicked the nociceptive behaviors as evidenced by decreased thermal and mechanical nociceptive threshold. Furthermore, we found that mature circRNA-Filip1l expression was negatively regulated by miRNA-1224 via binding and splicing of precursor of circRNA-Filip1l (pre-circRNA-Filip1l) in the Argonaute-2 (Ago2)-dependent manner. Increase of spinal circRNA-Filip1l expression resulted from the decrease of miRNA-1224 expression under chronic inflammation pain state. miRNA-1224 knockdown or Ago2 overexpression induced nociceptive behaviors in naive mice, which was prevented by the knockdown of spinal circRNA-Filip1l. Finally, we demonstrated that a ubiquitin protein ligase E3 component n-recognin 5 (Ubr5), validated as a target of circRNA-Filip1l, plays a pivotal role in regulation of nociception by spinal circRNA-Filip1l. These data suggest that miRNA-1224-mediated and Ago2-dependent modulation of spinal circRNA-Filip1l expression regulates nociception via targeting Ubr5, revealing a novel epigenetic mechanism of interaction between miRNA and circRNA in chronic inflammation pain. Significance StatementcircRNAs are emerging as new players in regulation of gene expression. Here, we found that the increase of circRNA-Filip1l mediated by miRNA-1224 in an Ago2-dependent way in the spinal cord is involved in regulation of nociception via targeting Ubr5. Our study reveals a novel epigenetic mechanism of interaction between miRNA and circRNA in chronic inflammation pain.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-1224 Splicing CircularRNA-Filip1l in an Ago2-Dependent Manner Regulates Chronic Inflammatory Pain via Targeting Ubr5

Pan

Sun

et al. 2019

J. Neurosci.

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“…A similar effect on inhibiting MPTP-induced apoptosis was observed by overexpressing miR-128 in mice . Dopamine receptors and the dopamine transporter have also been shown to be regulated by miRNA expression . It is, therefore, possible that the increased expression of protective miRNAs could be occurring in rrf-1 and rrf-3 mutants that are protecting the worms from MeHg-induced damage to dopaminergic signaling.…”

Section: Discussionmentioning

confidence: 73%

MicroRNA Expression Influences Methylmercury-Induced Lipid Accumulation and Mitochondrial Toxicity in Caenorhabditis elegans

Nielsen

Crawford

Martell

et al. 2021

Chem. Res. Toxicol.

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Metabolic effects of methylmercury (MeHg) are gaining wider attention. We have previously shown that MeHg causes lipid dysregulation in Caenorhabditis elegans (C. elegans), leading to altered gene expression, increased triglyceride levels and lipid storage, and altered feeding behaviors. Transcriptional regulators, such as transcription factors and microRNAs (miRNAs), have been shown to regulate lipid storage, serum triglycerides, and adipogenic gene expression in human and rodent models of metabolic diseases. As we recently investigated adipogenic transcription factors induced by MeHg, we were, therefore, interested in whether MeHg may also regulate miRNA sequences to cause metabolic dysfunction. Lipid dysregulation, as measured by triglyceride levels, lipid storage sites, and feeding behaviors, was assessed in wild-type (N2) worms and in transgenic worms that either were sensitive to miRNA expression or were unable to process miRNAs. Worms that were sensitive to the miRNA expression were protected from MeHg-induced lipid dysregulation. In contrast, the mutant worms that were unable to process miRNAs had exacerbated MeHg-induced lipid dysregulation. Concurrent with differential lipid homeostasis, miRNA-expression mutants had altered MeHg-induced mitochondrial toxicity as compared to N2, with the miRNA-sensitive mutants showing mitochondrial protection and the miRNA-processing mutants showing increased mitotoxicity. Taken together, our data demonstrate that the expression of miRNAs is an important determinant in MeHg toxicity and MeHg-induced metabolic dysfunction in C. elegans.

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“…In the last years, it has been becoming clear that ncRNA dysregulation plays a critical role in the etiology of human neurological disorders. Actually, ncRNAs have emerged as potentially important players in this field; even more recent studies underline their pivotal roles in several neurological disorders, among which are schizophrenia [ 107 ], addiction [ 108 , 109 ], and depression [ 110 ], as already summarized in these previous reviews. Here, we will specifically focus on the current advances in ncRNA research involvements in PD.…”

Section: Noncoding Rnas Regulatory Network In Neurological Diseasementioning

confidence: 99%

Noncoding RNAs and Midbrain DA Neurons: Novel Molecular Mechanisms and Therapeutic Targets in Health and Disease

et al. 2020

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Midbrain dopamine neurons have crucial functions in motor and emotional control and their degeneration leads to several neurological dysfunctions such as Parkinson’s disease, addiction, depression, schizophrenia, and others. Despite advances in the understanding of specific altered proteins and coding genes, little is known about cumulative changes in the transcriptional landscape of noncoding genes in midbrain dopamine neurons. Noncoding RNAs—specifically microRNAs and long noncoding RNAs—are emerging as crucial post-transcriptional regulators of gene expression in the brain. The identification of noncoding RNA networks underlying all stages of dopamine neuron development and plasticity is an essential step to deeply understand their physiological role and also their involvement in the etiology of dopaminergic diseases. Here, we provide an update about noncoding RNAs involved in dopaminergic development and metabolism, and the related evidence of these biomolecules for applications in potential treatments for dopaminergic neurodegeneration.

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Noncoding RNA Regulation of Dopamine Signaling in Diseases of the Central Nervous System

Cited by 15 publications

References 75 publications

MicroRNA-1224 Splicing CircularRNA-Filip1l in an Ago2-Dependent Manner Regulates Chronic Inflammatory Pain via Targeting Ubr5

MicroRNA-1224 Splicing CircularRNA-Filip1l in an Ago2-Dependent Manner Regulates Chronic Inflammatory Pain via Targeting Ubr5

MicroRNA Expression Influences Methylmercury-Induced Lipid Accumulation and Mitochondrial Toxicity in Caenorhabditis elegans

Noncoding RNAs and Midbrain DA Neurons: Novel Molecular Mechanisms and Therapeutic Targets in Health and Disease

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