1. ciRS-7 and miR-7 regulate ischemia-induced neuronal death via glutamatergic signaling.
- Author
-
Scoyni F, Sitnikova V, Giudice L, Korhonen P, Trevisan DM, Hernandez de Sande A, Gomez-Budia M, Giniatullina R, Ugidos IF, Dhungana H, Pistono C, Korvenlaita N, Välimäki NN, Kangas SM, Hiltunen AE, Gribchenko E, Kaikkonen-Määttä MU, Koistinaho J, Ylä-Herttuala S, Hinttala R, Venø MT, Su J, Stoffel M, Schaefer A, Rajewsky N, Kjems J, LaPierre MP, Piwecka M, Jolkkonen J, Giniatullin R, Hansen TB, and Malm T
- Subjects
- Mice, Animals, RNA, Untranslated, RNA, Circular, Signal Transduction, Ischemia, MicroRNAs genetics, MicroRNAs metabolism, RNA, Long Noncoding metabolism
- Abstract
Brain functionality relies on finely tuned regulation of gene expression by networks of non-coding RNAs (ncRNAs) such as the one composed by the circular RNA ciRS-7 (also known as CDR1as), the microRNA miR-7, and the long ncRNA Cyrano. We describe ischemia-induced alterations in the ncRNA network both in vitro and in vivo and in transgenic mice lacking ciRS-7 or miR-7. Our data show that cortical neurons downregulate ciRS-7 and Cyrano and upregulate miR-7 expression during ischemia. Mice lacking ciRS-7 exhibit reduced lesion size and motor impairment, while the absence of miR-7 alone results in increased ischemia-induced neuronal death. Moreover, miR-7 levels in pyramidal excitatory neurons regulate neurite morphology and glutamatergic signaling, suggesting a potential molecular link to the in vivo phenotype. Our data reveal the role of ciRS-7 and miR-7 in modulating ischemic stroke outcome, shedding light on the pathophysiological function of intracellular ncRNA networks in the brain., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF