Holm, AnjaAnjaHolmPossovre, Marie-LaureMarie-LaurePossovreBandarabadi, MojtabaMojtabaBandarabadiMoseholm, Kristine FKristine FMoseholmJustinussen, Jessica LJessica LJustinussenBozic, IvanIvanBozic0000-0002-3233-9936Lemcke, RenéRenéLemckeArribat, YoanYoanArribatAmati, FrancescaFrancescaAmatiSilahtaroglu, AsliAsliSilahtarogluJuventin, MaximeMaximeJuventinAdamantidis, Antoine RogerAntoine RogerAdamantidisTafti, MehdiMehdiTaftiKornum, Birgitte RBirgitte RKornum2024-10-092024-10-092022-04-26https://boris-portal.unibe.ch/handle/20.500.12422/70322SignificanceThe 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.enhypocretin miR-137 orexin sleep wake600 - Technology::610 - Medicine & healtharticle10.48350/1694633545231010.1073/pnas.2112225119