The evolutionarily conserved miRNA-137 targets the neuropeptide hypocretin/orexin and modulates the wake to sleep ratio.

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)

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 and 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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