Open AccessThe evolutionarily conserved miRNA-137 targets the neuropeptide hypocretin/orexin and modulates the wake to sleep ratio
Author(s) -
Anja Holm,
Marie-Laure Possovre,
Mojtaba Bandarabadi,
Kristine F. Moseholm,
J.L. Justinussen,
Ivan Bozic,
René Lemcke,
Yoan Arribat,
Francesca Amati,
Asli Silahtaroglu,
Maxime Juventin,
Antoine Adamantidis,
Mehdi Tafti,
Birgitte Rahbek Kornum
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2112225119
Subject(s) - wakefulness , orexin , narcolepsy , downregulation and upregulation , neuropeptide , gene knockdown , biology , orexin a , endogeny , endocrinology , medicine , microrna , microbiology and biotechnology , neuroscience , receptor , genetics , gene , electroencephalography , neurology
Significance The 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) andHcrt . We demonstrate that intracellular miR-137 levels in Hcrt neurons regulateHcrt 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 theMIR137 locus is genetically associated with sleep duration in humans. Together, our findings reveal an evolutionarily conserved sleep–wake regulatory role of miR-137.