Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function


  • M. Piwecka
  • P. Glažar
  • L.R. Hernandez-Miranda
  • S. Memczak
  • S.A. Wolf
  • A. Rybak-Wolf
  • A. Filipchyk
  • F. Klironomos
  • C.A. Cerda Jara
  • P. Fenske
  • T. Trimbuch
  • V. Zywitza
  • M. Plass
  • L. Schreyer
  • S. Ayoub
  • C. Kocks
  • R. Kühn
  • C. Rosenmund
  • C. Birchmeier
  • N. Rajewsky


  • Science


  • Science 357 (6357): eaam8526


  • Hundreds of circular RNAs (circRNAs) are highly abundant in mammalian brain, with oftentimes conserved expression. Here, we show that the circRNA Cdr1as is massively bound by miR-7 and miR-671 in the human and mouse brain. When the Cdr1as locus was removed from the mouse genome, knockout animals displayed impaired sensorimotor gating, a deficit in the ability to filter out unnecessary information associated with neuropsychiatric disorders. Electrophysiological recordings revealed dysfunctional synaptic transmission. Expression of microRNAs miR-7 and miR-671 was specifically and post-transcriptionally misregulated in all brain regions analyzed. Expression of immediate early genes such as Fos, a direct miR-7 target, was enhanced in Cdr1as-deficient brains, providing a possible molecular link to the behavioral phenotype. Our data indicate an in vivo loss-of-function circRNA phenotype and suggest that interactions between circRNAs and miRNAs are important for normal brain function.