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ciRS-7 and miR-7 regulate ischemia-induced neuronal death via glutamatergic signaling

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Item Type:Article
Title:ciRS-7 and miR-7 regulate ischemia-induced neuronal death via glutamatergic signaling
Creators Name:Scoyni, F. and Sitnikova, V. and Giudice, L. and Korhonen, P. and Trevisan, D.M. and Hernandez de Sande, A. and Gomez-Budia, M. and Giniatullina, R. and Ugidos, I.F. and Dhungana, H. and Pistono, C. and Korvenlaita, N. and Välimäki, N.N. and Kangas, S.M. and Hiltunen, A.E. and Gribchenko, E. and Kaikkonen-Määttä, M.U. and Koistinaho, J. and Ylä-Herttuala, S. and Hinttala, R. and Venø, M.T. and Su, J. and Stoffel, M. and Schaefer, A. and Rajewsky, N. and Kjems, J. and LaPierre, M.P. and Piwecka, M. and Jolkkonen, J. and Giniatullin, R. and Hansen, T.B. and Malm, T.
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.
Keywords:non-Coding RNAs, Ischemic Stroke, microRNAs, circularRNAs, Molecular Networks, Post-Transcriptional Regulation, Glutamate, Excitotoxicity, Cell Death, Animals, Mice
Source:Cell Reports
Publisher:Cell Press / Elsevier
Page Range:113862
Date:26 March 2024
Official Publication:https://doi.org/10.1016/j.celrep.2024.113862
PubMed:View item in PubMed

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