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
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SignificanceThe hypocretin (Hcrt, also known as orexin) neuropeptides regulate sleep and wake stability, and disturbances of Hcrt can lead to sleep disorders. MicroRNAs (miRNAs) are short noncoding RNAs that fine-tune protein expression levels, and miRNA-based therapeutics are emerging. We report a functional interaction between miRNA (miR-137) and Hcrt. We demonstrate that intracellular miR-137 levels in Hcrt neurons regulate Hcrt expression with downstream effects on wakefulness. Specifically, lowering of miR-137 levels increased wakefulness in mice. We further show that the miR-137:Hcrt interaction is conserved across mice and humans, that miR-137 also regulates sleep-wake balance in zebrafish, and that the MIR137 locus is genetically associated with sleep duration in humans. Together, our findings reveal an evolutionarily conserved sleep-wake regulatory role of miR-137.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Unit Sahli Building > Forschungsgruppe Neurologie 04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology |
UniBE Contributor: |
Bozic, Ivan, Adamantidis, Antoine Roger |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
0027-8424 |
Publisher: |
National Academy of Sciences NAS |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
25 Apr 2022 10:08 |
Last Modified: |
05 Dec 2022 16:19 |
Publisher DOI: |
10.1073/pnas.2112225119 |
PubMed ID: |
35452310 |
Uncontrolled Keywords: |
hypocretin miR-137 orexin sleep wake |
BORIS DOI: |
10.48350/169463 |
URI: |
https://boris.unibe.ch/id/eprint/169463 |
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