The evolutionarily conserved miRNA-137 targets the neuropeptide hypocretin/orexin and modulates the wake to sleep ratio
Authors:
- Anja HolmAHAnja Holm
- Marie-Laure PossovreMPMarie-Laure Possovre
- Mojtaba BandarabadiMBMojtaba Bandarabadi
- Kristine F. MoseholmKMKristine F. Moseholm
- Jessica L. JustinussenJJJessica L. Justinussen
- Ivan BozicIBIvan Bozic
- René LemckeRLRené Lemcke
- Yoan ArribatYAYoan Arribat
- Francesca AmatiFAFrancesca Amati
- Asli SilahtarogluAsli Silahtaroglu
- Maxime JuventinMJMaxime Juventin
- Antoine AdamantidisAAAntoine Adamantidis
Open Access
- 22 April 2022
- journal article
- research article
- Published by National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 119 (17)
Abstract
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) 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.Keywords
This publication has 56 references indexed in Scilit:
- Translational profiling of hypocretin neurons identifies candidate molecules for sleep regulationGenes & Development, 2013
- Chromosome 1p21.3 microdeletions comprising DPYD and MIR137 are associated with intellectual disabilityJournal of Medical Genetics, 2011
- MicroRNA 132 alters sleep and varies with time in brainJournal of Applied Physiology, 2011
- The microRNA body map: dissecting microRNA function through integrative genomicsNucleic Acids Research, 2011
- Tumor necrosis factor-alpha regulates the Hypocretin system via mRNA degradation and ubiquitinationBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2011
- miRNA-132 orchestrates chromatin remodeling and translational control of the circadian clockHuman Molecular Genetics, 2010
- MicroRNA miR-137 Regulates Neuronal Maturation by Targeting Ubiquitin Ligase Mind Bomb-1Stem Cells, 2010
- Cross talk between microRNA and epigenetic regulation in adult neurogenesisJournal of Cell Biology, 2010
- Sleep problems in Rett syndromeBrain and Development, 2007
- A Mammalian microRNA Expression Atlas Based on Small RNA Library SequencingCell, 2007