Malin Akerblom

Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function
Piwecka M1, Glažar P1, Hernandez-Miranda LR2, Memczak S1,3, Wolf SA4, Rybak-Wolf A1, Filipchyk A1, Klironomos F1, Cerda Jara CA1, Fenske P5, Trimbuch T5, Zywitza V1, Plass M1, Schreyer L1, Ayoub S1, Kocks C1, Kühn R6,7, Rosenmund C5, Birchmeier C2, Rajewsky N8.
Science. 2017 Aug 10. pii: eaam8526. doi: 10.1126/science.aam8526. [Epub ahead of print]
August 10, 2017
Laboratory for Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str. 10, Berlin-Buch, Germany. Laboratory for Developmental Biology and Signal Transduction, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str. 10, Berlin-Buch, Germany. Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max Delbrück Center for Molecular Medicine, Berlin, Germany. Laboratory for Cellular Neurosciences, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str. 10, Berlin-Buch, Germany. Department of Neurophysiology, NeuroCure Cluster of Excellence, Charité-Universitätsmedizin, Berlin, Germany. Transgenic Core Facility, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str. 10, Berlin-Buch, Germany. Berlin Institute of Health, Kapelle-Ufer 2, Berlin, Germany. Laboratory for Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str. 10, Berlin-Buch, Germany. [email protected]
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.
Date: 
August 23, 2017
Where: 
HSW 1057 at noon