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

• DOI: 10.1126/science.aam8526
• Publication Date: 2017-08-11T00:50:19Z
• Authors: Monika Piwecka; Petar Glažar; Luis R. Hernandez...; Sebastian Memczak; Susanne A. Wolf; Agnieszka Rybak-Wolf; Andrei Filipchyk; Filippos Klironomos; Cledi Alicia Cerd...; Pascal Fenske; Thorsten Trimbuch; Vera Zywitza; Mireya Plass; Luisa Schreyer; Salah Ayoub; Christine Kocks; Ralf Kühn; Christian Rosenmund; Carmen Birchmeier; Nikolaus Rajewsky
• Keywords: Mice, Knockout; 0301 basic medicine; Behavior, Animal; RNA Stability; Brain; RNA, Circular; Up-Regulation; 3. Good health; Mice; MicroRNAs; 03 medical and health sciences; Genetic Loci; Animals; Humans; RNA; RNA, Long Noncoding; CRISPR-Cas Systems; RNA Processing, Post-Transcriptional

Cutting out circular RNAs

Circular RNAs are widespread, but their functions have been controversial. Piwecka et al. used CRISPR-Cas9 technology to remove the locus encoding the circular RNA Cdr1as from the mouse genome. Single-cell electrophysiological measurements in excitatory neurons revealed an increase in spontaneous vesicle release from the knockout mice and depression in the synaptic response with two consecutive stimuli, indicating that Cdr1as deficiency leads to dysfunction of excitatory synaptic transmission. Small RNA sequencing of several major regions of the brain showed that expression of two microRNAs, miR-7 and miR-671, that bind to Cdr1as decreased and increased, respectively. These results, along with expression analyses, suggest that neuronal Cdr1as stabilizes or transports miR-7, which in turn represses genes that are early responders to different stimuli.

Science , this issue p. eaam8526