학술논문
ciRS-7 and miR-7 regulate ischemia-induced neuronal death via glutamatergic signaling
Document Type
article
Author
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
Source
Cell Reports, Vol 43, Iss 3, Pp 113862- (2024)
Subject
Language
English
ISSN
2211-1247
Abstract
Summary: 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.