The evolutionarily conserved miRNA-137 targets the neuropeptide hypocretin/orexin and modulates the wake to sleep ratio
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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.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 119, No. 17, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The evolutionarily conserved miRNA-137 targets the neuropeptide hypocretin/orexin and modulates the wake to sleep ratio
AU - Holm, Anja
AU - Possovre, Marie Laure
AU - Bandarabadi, Mojtaba
AU - Moseholm, Kristine F.
AU - Justinussen, Jessica L.
AU - Bozic, Ivan
AU - Lemcke, René
AU - Arribat, Yoan
AU - Amati, Francesca
AU - Silahtaroglu, Asli
AU - Juventin, Maxime
AU - Adamantidis, Antoine
AU - Tafti, Mehdi
AU - Kornum, Birgitte R.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - hypocretin
KW - miR-137
KW - orexin
KW - sleep
KW - wake
U2 - 10.1073/pnas.2112225119
DO - 10.1073/pnas.2112225119
M3 - Journal article
C2 - 35452310
AN - SCOPUS:85129778441
VL - 119
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 17
ER -
ID: 306698128