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


  • F. Scoyni
  • V. Sitnikova
  • L. Giudice
  • P. Korhonen
  • D.M. Trevisan
  • A. Hernandez de Sande
  • M. Gomez-Budia
  • R. Giniatullina
  • I.F. Ugidos
  • H. Dhungana
  • C. Pistono
  • N. Korvenlaita
  • N.N. Välimäki
  • S.M. Kangas
  • A.E. Hiltunen
  • E. Gribchenko
  • M.U. Kaikkonen-Määttä
  • J. Koistinaho
  • S. Ylä-Herttuala
  • R. Hinttala
  • M.T. Venø
  • J. Su
  • M. Stoffel
  • A. Schaefer
  • N. Rajewsky
  • J. Kjems
  • M.P. LaPierre
  • M. Piwecka
  • J. Jolkkonen
  • R. Giniatullin
  • T.B. Hansen
  • T. Malm


  • Cell Reports


  • Cell Rep 43 (3): 113862


  • 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.