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

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 HinttalaMorten 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*

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

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.

Original languageEnglish
Article number113862
JournalCell Reports
Volume43
Issue3
Number of pages24
ISSN2211-1247
DOIs
Publication statusPublished - Mar 2024

Keywords

  • cell death
  • circularRNAs
  • CP: Neuroscience
  • excitotoxicity
  • glutamate
  • ischemic stroke
  • microRNAs
  • molecular networks
  • non-coding RNAs
  • post-transcriptional regulation

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