The evolutionarily conserved miRNA-137 targets the neuropeptide hypocretin/orexin and modulates the wake to sleep ratio
| Autor: | Anja Holm, Marie-Laure Possovre, Mojtaba Bandarabadi, Kristine F. Moseholm, Jessica L. Justinussen, Ivan Bozic, René Lemcke, Yoan Arribat, Francesca Amati, Asli Silahtaroglu, Maxime Juventin, Antoine Adamantidis, Mehdi Tafti, Birgitte R. Kornum |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
610 Medicine & health
miR-137 Mice Wakefulness/genetics Zebrafish/metabolism Animals Intracellular Signaling Peptides and Proteins/genetics MicroRNAs/genetics Neuropeptides/metabolism Orexins/genetics Orexins/metabolism Sleep/genetics hypocretin orexin sleep wake Wakefulness Zebrafish Orexins Multidisciplinary Neuropeptides Intracellular Signaling Peptides and Proteins MicroRNAs Sleep 610 Medizin und Gesundheit psychological phenomena and processes |
| Zdroj: | Holm, Anja; Possovre, Marie-Laure; Bandarabadi, Mojtaba; Moseholm, Kristine F; Justinussen, Jessica L; Bozic, Ivan; Lemcke, René; Arribat, Yoan; Amati, Francesca; Silahtaroglu, Asli; Juventin, Maxime; Adamantidis, Antoine; Tafti, Mehdi; Kornum, Birgitte R (2022). The evolutionarily conserved miRNA-137 targets the neuropeptide hypocretin/orexin and modulates the wake to sleep ratio. Proceedings of the National Academy of Sciences of the United States of America-PNAS, 119(17), e2112225119. National Academy of Sciences NAS 10.1073/pnas.2112225119 Holm, A, Possovre, M-L, Bandarabadi, M, Moseholm, K F, Justinussen, J L, Bozic, I, Lemcke, R, Arribat, Y, Amati, F, Silahtaroglu, A, Juventin, M, Adamantidis, A, Tafti, M & Kornum, B R 2022, ' The evolutionarily conserved miRNA-137 targets the neuropeptide hypocretin/orexin and modulates the wake to sleep ratio ', Proceedings of the National Academy of Sciences of the United States of America, vol. 119, no. 17, e2112225119, pp. e2112225119 . https://doi.org/10.1073/pnas.2112225119 Holm, A, Possovre, M L, Bandarabadi, M, Moseholm, K F, Justinussen, J L, Bozic, I, Lemcke, R, Arribat, Y, Amati, F, Silahtaroglu, A, Juventin, M, Adamantidis, A, Tafti, M & Kornum, B R 2022, ' The evolutionarily conserved miRNA-137 targets the neuropeptide hypocretin/orexin and modulates the wake to sleep ratio ', Proceedings of the National Academy of Sciences of the United States of America, vol. 119, no. 17 . https://doi.org/10.1073/pnas.2112225119 Proceedings of the National Academy of Sciences of the United States of America, vol. 119, no. 17, pp. e2112225119 |
| DOI: | 10.1073/pnas.2112225119 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|