ArticleProceedings of the National Academy of Sciences of the United States of America2022
The evolutionarily conserved miRNA-137 targets the neuropeptide hypocretin/orexin and modulates the wake to sleep ratio.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 31 citations in OpenAlex.
- Scoping review on the relationship between microRNAs (miRNAs) and short sleep disorder or insomnia with short sleep duration.Sleep medicine: X · 2026Article
- Epigenetic Insights and Exosome-Based Therapeutics for Insomnia: Bridging Sleep Biology and Precision Medicine.Molecular neurobiology · 2026Review
- Targeting the Orexin System in the Pharmacological Management of Insomnia and Other Diseases: Suvorexant, Lemborexant, Daridorexant, and Novel Experimental Agents.International journal of molecular sciences · 2025Review
- Hypersomnolence in focus: a white paper of the 6th Think Tank World Sleep Forum.Sleep medicine · 2025Review
- Current knowledge on the pathophysiology of idiopathic hypersomnia and potential mechanisms of action for low-sodium oxybate treatment.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2025Review
- Genome-wide, integrative analysis implicates exosome-derived microRNA dysregulation in chronic insomnia.Sleep · 2025Article
- MicroRNAs as Epigenetic Biomarkers of Pathogenetic Mechanisms of the Metabolic Syndrome Induced by Antiseizure Medications: Systematic Review.Journal of clinical medicine · 2025Review
- Decoding Multifaceted Roles of Sleep-Related Genes as Molecular Bridges in Chronic Disease Pathogenesis.International journal of molecular sciences · 2025Review
- Light-regulated microRNAs shape dynamic gene expression in the zebrafish circadian clock.PLoS genetics · 2025Article
- Article
- CorticalProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Epigenetic silencing of selected hypothalamic neuropeptides in narcolepsy with cataplexy.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The role of microRNAs in the molecular link between circadian rhythm and autism spectrum disorder.Animal cells and systems · 2023Review
- miR-137: A therapeutic candidate or a key molecular regulator in Alzheimer's disease?Journal of Alzheimer's disease reportsReview
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypocretin (Hcrt), also known as orexin, neuropeptide signaling stabilizes sleep and wakefulness in all vertebrates. A lack of Hcrt causes the sleep disorder narcolepsy, and increased Hcrt signaling has been speculated to cause insomnia, but while the signaling pathways of Hcrt are relatively well-described, the intracellular mechanisms that regulate its expression remain unclear. Here, we tested the role of microRNAs (miRNAs) in regulating Hcrt expression. We found that miR-137, miR-637, and miR-654-5p target the human HCRT gene. miR-137 is evolutionarily conserved and also targets mouse Hcrt as does miR-665. Inhibition of miR-137 specifically in Hcrt neurons resulted in Hcrt upregulation, longer episodes of wakefulness, and significantly longer wake bouts in the first 4 h of the active phase. IL-13 stimulation upregulated endogenous miR-137, while Hcrt mRNA decreased both in vitro and in vivo. Furthermore, knockdown of miR-137 in zebrafish substantially increased wakefulness. Finally, we show that in humans, the MIR137 locus is genetically associated with sleep duration. In conclusion, these results show that an evolutionarily conserved miR-137:Hcrt interaction is involved in sleep–wake regulation.
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