Cell Reports (Mar 2024)
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 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
Affiliations
- Flavia Scoyni
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70221 Kuopio, Finland; Corresponding author
- Valeriia Sitnikova
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70221 Kuopio, Finland
- Luca Giudice
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70221 Kuopio, Finland
- Paula Korhonen
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70221 Kuopio, Finland
- Davide M. Trevisan
- Department of Biosciences and Nutrition, Karolinska Institute, 17177 Stockholm, Sweden
- Ana Hernandez de Sande
- School of Medicine, University of Eastern Finland, 70221 Kuopio, Finland
- Mireia Gomez-Budia
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70221 Kuopio, Finland
- Raisa Giniatullina
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70221 Kuopio, Finland
- Irene F. Ugidos
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70221 Kuopio, Finland
- Hiramani Dhungana
- Neuroscience Center, University of Helsinki, 00290 Helsinki, Finland
- Cristiana Pistono
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70221 Kuopio, Finland
- Nea Korvenlaita
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70221 Kuopio, Finland
- Nelli-Noora Välimäki
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70221 Kuopio, Finland
- Salla M. Kangas
- Biocenter Oulu, University of Oulu, 90014 Oulu, Finland
- Anniina E. Hiltunen
- Medical Research Center Oulu and Research Unit of Clinical Medicine, University of Oulu and Oulu University Hospital, 90014 Oulu, Finland
- Emma Gribchenko
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70221 Kuopio, Finland
- Minna U. Kaikkonen-Määttä
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70221 Kuopio, Finland
- Jari Koistinaho
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70221 Kuopio, Finland; Neuroscience Center, University of Helsinki, 00290 Helsinki, Finland
- Seppo Ylä-Herttuala
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70221 Kuopio, Finland
- Reetta Hinttala
- Biocenter Oulu, University of Oulu, 90014 Oulu, Finland; Medical Research Center Oulu and Research Unit of Clinical Medicine, University of Oulu and Oulu University Hospital, 90014 Oulu, Finland
- Morten T. Venø
- Omiics ApS, 8200 Aarhus, Denmark; Interdisciplinary Nanoscience Center, Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus, Denmark
- Junyi Su
- Interdisciplinary Nanoscience Center, Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus, Denmark
- Markus Stoffel
- Institute of Molecular Health Sciences, ETH Zurich, 8093 Zürich, Switzerland
- Anne Schaefer
- Departments of Neuroscience and Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029-6504, USA; Max Planck Institute, Biology of Ageing, 50931 Cologne, Germany
- Nikolaus Rajewsky
- Systems Biology of Gene Regulatory Elements, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin Institute for Medical Systems Biology (BIMSB), 10115 Berlin, Germany
- Jørgen Kjems
- Interdisciplinary Nanoscience Center, Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus, Denmark
- Mary P. LaPierre
- Institute of Molecular Health Sciences, ETH Zurich, 8093 Zürich, Switzerland
- Monika Piwecka
- Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704 Poznan, Poland
- Jukka Jolkkonen
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70221 Kuopio, Finland
- Rashid Giniatullin
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70221 Kuopio, Finland
- Thomas B. Hansen
- Interdisciplinary Nanoscience Center, Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus, Denmark
- Tarja Malm
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70221 Kuopio, Finland; Corresponding author
- Journal volume & issue
-
Vol. 43,
no. 3
p. 113862
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.
