ciRS-7 and miR-7 regulate ischemia-induced neuronal death via glutamatergic signaling
Scoyni, Flavia; Sitnikova, Valeriia; Giudice, Luca; Korhonen, Paula; Trevisan, Davide M; Hernandez de Sande, Ana; Gomez-Budia, Mireia; Giniatullina, Raisa; Ugidos, Irene F; Dhungana, Hiramani; Pistono, Cristiana; Korvenlaita, Nea; Välimäki, Nelli-Noora; Kangas, Salla M; Hiltunen, Anniina E; Gribchenko, Emma; Kaikkonen-Määttä, Minna U; Koistinaho, Jari; Ylä-Herttuala, Seppo; Hinttala, Reetta; Venø, Morten T; Su, Junyi; Stoffel, Markus; Schaefer, Anne; Rajewsky, Nikolaus; Kjems, Jørgen; LaPierre, Mary P; Piwecka, Monika; Jolkkonen, Jukka; Giniatullin, Rashid; Hansen, Thomas B; Malm, Tarja (2024-03-05)
Flavia Scoyni, Valeriia Sitnikova, Luca Giudice, Paula Korhonen, Davide M. Trevisan, Ana Hernandez de Sande, Mireia Gomez-Budia, Raisa Giniatullina, Irene F. Ugidos, Hiramani Dhungana, Cristiana Pistono, Nea Korvenlaita, Nelli-Noora Välimäki, Salla M. Kangas, Anniina E. Hiltunen, Emma Gribchenko, Minna U. Kaikkonen-Määttä, Jari Koistinaho, Seppo Ylä-Herttuala, Reetta Hinttala, Morten T. Venø, Junyi Su, Markus Stoffel, Anne Schaefer, Nikolaus Rajewsky, Jørgen Kjems, Mary P. LaPierre, Monika Piwecka, Jukka Jolkkonen, Rashid Giniatullin, Thomas B. Hansen, Tarja Malm, ciRS-7 and miR-7 regulate ischemia-induced neuronal death via glutamatergic signaling, Cell Reports, Volume 43, Issue 3, 2024, 113862, ISSN 2211-1247, https://doi.org/10.1016/j.celrep.2024.113862
© 2024 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
https://creativecommons.org/licenses/by-nc-nd/4.0/
https://urn.fi/URN:NBN:fi:oulu-202404032530
Tiivistelmä
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.
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