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| Item Type: | Article |
|---|---|
| Title: | Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function |
| Creators: |
Piwecka, M.  ORCID: https://orcid.org/0000-0003-4104-6577, Glažar, P. ORCID: https://orcid.org/0000-0003-0842-0088, Hernandez-Miranda, L.R. ORCID: https://orcid.org/0000-0002-0498-708X, Memczak, S. ORCID: https://orcid.org/0000-0001-9518-7135, Wolf, S.A. ORCID: https://orcid.org/0000-0003-0922-8418, Rybak-Wolf, A. ORCID: https://orcid.org/0000-0002-1192-5290, Filipchyk, A. ORCID: https://orcid.org/0000-0002-2029-8460, Klironomos, F., Cerda Jara, C.A. ORCID: https://orcid.org/0000-0003-1783-5533, Fenske, P., Trimbuch, T. ORCID: https://orcid.org/0000-0001-7512-8955, Zywitza, V. ORCID: https://orcid.org/0000-0003-3055-8569, Plass, M. ORCID: https://orcid.org/0000-0002-9891-2723, Schreyer, L., Ayoub, S. ORCID: https://orcid.org/0000-0001-5043-8922, Kocks, C. ORCID: https://orcid.org/0000-0003-1749-3334, Kühn, R. ORCID: https://orcid.org/0000-0003-1694-9803, Rosenmund, C. ORCID: https://orcid.org/0000-0002-3905-2444, Birchmeier, C. ORCID: https://orcid.org/0000-0002-2041-8872 and Rajewsky, N. ORCID: https://orcid.org/0000-0002-4785-4332
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| Abstract: | 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. |
| Keywords: | Behavior, Animal, Brain, CRISPR-Cas Systems, Genetic Loci, MicroRNAs, RNA, RNA Processing, Post-Transcriptional, RNA Stability, RNA, Long Noncoding, Up-Regulation, Animals, Mice, Mice, Knockout |
| Source: | Science |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Volume: | 357 |
| Number: | 6357 |
| Page Range: | eaam8526 |
| Date: | 22 September 2017 |
| Official Publication: | https://doi.org/10.1126/science.aam8526 |
| PubMed: | View item in PubMed |
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