Laboratory for Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Straße 10, Berlin-Buch, Germany.
Laboratory for Developmental Biology and Signal Transduction, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Straße 10, Berlin-Buch, Germany.
Science. 2017 Sep 22;357(6357). doi: 10.1126/science.aam8526. Epub 2017 Aug 10.
Hundreds of circular RNAs (circRNAs) are highly abundant in the mammalian brain, often with conserved expression. Here we show that the circRNA Cdr1as is massively bound by the microRNAs (miRNAs) miR-7 and miR-671 in human and mouse brains. When the locus was removed from the mouse genome, knockout animals displayed impaired sensorimotor gating-a deficit in the ability to filter out unnecessary information-which is associated with neuropsychiatric disorders. Electrophysiological recordings revealed dysfunctional synaptic transmission. Expression of miR-7 and miR-671 was specifically and posttranscriptionally misregulated in all brain regions analyzed. Expression of immediate early genes such as , a direct miR-7 target, was enhanced in -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 Cdr1as and miRNAs are important for normal brain function.
数百种环状 RNA（circRNA）在哺乳动物脑中高度丰富，通常具有保守的表达。在这里，我们表明环状 RNA Cdr1as 大量结合了人类和小鼠脑中的 microRNAs（miRNAs）miR-7 和 miR-671。当从小鼠基因组中删除 基因座时，敲除动物表现出感觉运动门控受损-一种过滤掉不必要信息的能力缺陷-这与神经精神疾病有关。电生理记录显示突触传递功能障碍。在分析的所有大脑区域中，miR-7 和 miR-671 的表达都出现了特异性和转录后失调。直接 miR-7 靶基因如 的即时早期基因表达增强，为行为表型提供了可能的分子联系。我们的数据表明体内功能丧失环状 RNA 表型，并表明 Cdr1as 和 miRNAs 之间的相互作用对于正常的大脑功能很重要。
