Nuclear microRNAs may regulate mitochondrial gene expression following effluent exposure in darter (Etheostoma) species

Robichaud, Karyn; Craig, Paul M.

doi:10.1016/j.cbpb.2022.110754

Cited by 3 publications

(2 citation statements)

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“…In fish, miRNAs regulate a variety of genes in response to stressors (Hung et al, 2016; Ikert & Craig, 2020; Zhou et al, 2019) by binding to their target mRNA 3′ untranslated region through the assistance of the RNA‐induced silencing complex (RISC), and canonically suppressing target protein expression or degrading target mRNA (Wightman et al, 1993; Zeng et al, 2003). Although miRNAs are known to act on nuclear mRNA, they are also present in the mitochondria of cells, where they regulate mitochondrial genes (Bandiera et al, 2011; Das et al, 2012; Zhuang et al, 2020), including in fish (Robichaud & Craig, 2022). Mitochondrial genes that encode subunits of the OXPHOS protein subunits, tRNAs, and rRNAs are derived from circular DNA that is unique to the mitochondria (Broughton et al, 2001; Satoh et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

“…Other RNAs involved in OXPHOS and mitochondrial transcription are transported into mitochondria, and it is hypothesized that miRNA are similarly transported into the mitochondria with argonaute RISC catalytic component 2 (Ago2; a protein involved in the RISC that solicits binding of miRNA to mRNA), where they can bind to and regulate mitochondrial RNA translation (Bandiera et al, 2011). Once they enter the mitochondria, the mitochondrial miRNAs (mitomiRs) have demonstrable effects in mammalian cells (Bandiera et al, 2011; Das et al, 2012; Zhuang et al, 2020), and predicted targets in fish (Ma et al, 2015; Robichaud & Craig, 2022).…”

Section: Introductionmentioning

confidence: 99%

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Venlafaxine exposure alters mitochondrial respiration and mitomiR abundance in zebrafish brains

Robichaud,

Bragg,

Servos

et al. 2024

Enviro Toxic and Chemistry

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Wastewater treatment plant (WWTP) effluent often releases pharmaceuticals like venlafaxine (a serotonin–norephinephrine reuptake inhibitor antidepressant) to freshwater ecosystems at levels causing adverse metabolic effects on fish. Changes to fish metabolism can be regulated by epigenetic mechanisms like microRNA (small RNA molecules that regulate mRNA translation), including regulating mitochondrial mRNAs. Nuclear‐encoded microRNAs regulate mitochondrial gene expression in mammals, and have predicted effects in fish. We aimed to identify whether venlafaxine exposure changed mitochondrial respiration and resulted in differentially abundant mitochondrial microRNA (mitomiRs) in zebrafish brains. In vitro exposure of brain homogenate to below environmentally relevant concentrations of venlafaxine (<1 µg/L) caused a decrease in mitochondrial respiration, although this was not driven by changes to mitochondrial Complex I or II function. To identify whether these effects occur in vivo, zebrafish were exposed to 1 µg/L venlafaxine for 0, 1, 6, 12, 24, and 96 h. In vivo, venlafaxine exposure had no significant effects on brain mitochondrial respiration; however, select mitomiRs (dre‐miR‐301a‐5p, dre‐miR‐301b‐3p, and dre‐miR‐301c‐3p) were also measured, because they were bioinformatically predicted to regulate mitochondrial cytochrome c oxidase subunit I (COI) abundance. These mitomiRs were differentially regulated based on venlafaxine exposure (with miR‐301c‐3p abundance differing during the day and miR‐301b‐3p being lower in exposed fish at night), and with respect to sex and time sampled. Overall, the results demonstrated that in vitro venlafaxine exposure to zebrafish brain caused a decrease in mitochondrial respiration, but these effects were not seen after acute in vivo exposure. Results may have differed because in vivo exposure allows for fish to mitigate effects through mechanisms that could include mitomiR regulation, and because fish were only acutely exposed. Environ Toxicol Chem 2024;00:1–14. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Venlafaxine exposure alters mitochondrial respiration and mitomiR abundance in zebrafish brains

Robichaud,

Bragg,

Servos

et al. 2024

Enviro Toxic and Chemistry

Self Cite

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Mitochondrial microRNA profiles are altered in thirteen-lined ground squirrels (Ictidomys tridecemlineatus) during hibernation

Robichaud,

Duffy,

Staples

et al. 2024

Physiological Genomics

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Thirteen-lined ground squirrels (TLGS) are obligate hibernators that cycle between torpor (low metabolic rate and body temperature) and interbout euthermia (IBE; typical euthermic body temperature and metabolism) from late autumn to spring. Many physiological changes occur throughout hibernation, including a reduction in liver mitochondrial metabolism during torpor, which is reversed during arousal to interbout euthermia. Nuclear-encoded microRNA (small post-transcriptional regulator molecules) differ in abundance throughout TLGS hibernation and have been shown to regulate mitochondrial gene expression in mammalian cell culture (where they are referred to as mitomiRs). This study characterized differences in mitomiR profiles from TLGS liver mitochondria isolated during summer, torpor, and IBE, and predicted their mitochondrial targets. Using small RNA sequencing, differentially abundant mitomiRs were identified between hibernation states and, using qPCR analysis we quantified expression of predicted mitochondrial mRNA targets. Most differences in mitomiR abundances were seasonal (i.e. between summer and winter) with only one mitomiR differentially abundant between IBE and torpor. Multiple factor analysis revealed three clusters divided by hibernation states, where clustering was predominantly driven by mitomiR abundances. Nine of these differentially abundant mitomiRs had predicted mitochondrial RNA targets, including subunits of electron transfer system complexes I and IV, 12S rRNA and two tRNAs. Overall, mitomiRs were predicted to suppress expression of their mitochondrial targets and may have some involvement in regulating protein translation in mitochondria. This study found differences in mitomiR abundances between seasons and hibernation states of TLGS and suggests potential mechanisms in regulating the mitochondrial electron transfer system.

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The dual role of microRNA (miR)-20b in cancers: Friend or foe?

et al. 2023

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MicroRNAs, as non-coding transcripts, modulate gene expression through RNA silencing under normal physiological conditions. Their aberrant expression has strongly associated with tumorigenesis and cancer development. MiR-20b is one of the crucial miRNAs that regulate essential biological processes such as cell proliferation, apoptosis, autophagy, and migration. Deregulated levels of miR-20b contribute to the early- and advanced stages of cancer. On the other hand, investigations emphasize the tumor suppressor ability of miR-20b. High-throughput strategies are developed to identify miR-20b potential targets, providing the proper insight into its molecular mechanism of action. Moreover, accumulated results suggest that miR-20b exerts its effects through diverse signaling pathways, including PI3K/AKT/mTOR and ERK axes. Restoration of the altered expression levels of miR-20b induces cell apoptosis and reduces invasion and migration. Further, miR-20b can be used as a biomarker in cancer. The current comprehensive review could lead to a better understanding of the miR-20b in either tumorigenesis or tumor regression that may open new avenues for cancer treatment.

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Nuclear microRNAs may regulate mitochondrial gene expression following effluent exposure in darter (Etheostoma) species

Cited by 3 publications

References 43 publications

Venlafaxine exposure alters mitochondrial respiration and mitomiR abundance in zebrafish brains

Venlafaxine exposure alters mitochondrial respiration and mitomiR abundance in zebrafish brains

Mitochondrial microRNA profiles are altered in thirteen-lined ground squirrels (Ictidomys tridecemlineatus) during hibernation

The dual role of microRNA (miR)-20b in cancers: Friend or foe?

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