PUBLICATION
The evolutionarily conserved miRNA-137 targets the neuropeptide hypocretin/orexin and modulates the wake to sleep ratio
- Authors
- 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.
- ID
- ZDB-PUB-220423-15
- Date
- 2022
- Source
- Proceedings of the National Academy of Sciences of the United States of America 119: e2112225119 (Journal)
- Registered Authors
- Amati, Francesca, Arribat, Yoan
- Keywords
- hypocretin, miR-137, orexin, sleep, wake
- MeSH Terms
-
- Animals
- Intracellular Signaling Peptides and Proteins/genetics
- Mice
- MicroRNAs*/genetics
- Neuropeptides*/metabolism
- Orexins/genetics
- Orexins/metabolism
- Sleep/genetics
- Wakefulness/genetics
- Zebrafish/metabolism
- PubMed
- 35452310 Full text @ Proc. Natl. Acad. Sci. USA
Citation
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. 119:e2112225119.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping