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

被引：1345

作者：

Piwecka, Monika ^{[1
]}

Glazar, Petar ^{[1
]}

Hernandez-Miranda, Luis R. ^{[2
]}

Memczak, Sebastian ^{[1
,3
,4
]}

Wolf, Susanne A. ^{[5
]}

Rybak-Wolf, Agnieszka ^{[1
]}

Filipchyk, Andrei ^{[1
]}

Klironomos, Filippos ^{[1
]}

Jara, Cledi Alicia Cerda ^{[1
]}

Fenske, Pascal ^{[6
]}

Trimbuch, Thorsten ^{[6
]}

Zywitza, Vera ^{[1
]}

Plass, Mireya ^{[1
]}

Schreyer, Luisa ^{[1
]}

Ayoub, Salah ^{[1
]}

Kocks, Christine ^{[1
]}

Kuhn, Ralf ^{[7
,8
]}

Rosenmund, Christian

Birchmeier, Carmen ^{[2
]}

Rajewsky, Nikolaus ^{[1
]}

机构：

[1] Max Delbruck Ctr Mol Med, Berlin Inst Med Syst Biol, Lab Syst Biol Gene Regulatory Elements, Robert Rossle Str 10, Berlin, Germany

[2] Max Delbruck Ctr Mol Med, Lab Dev Biol & Signal Transduct, Robert Rossle Str 10, Berlin, Germany

[3] Charite Med Fac, Expt & Clin Res Ctr, Robert Rossle Str 10, Berlin, Germany

[4] Max Delbruck Ctr Mol Med, Robert Rossle Str 10, Berlin, Germany

[5] Max Delbruck Ctr Mol Med, Lab Cellular Neurosci, Robert Rossle Str 10, Berlin, Germany

[6] Charite, NeuroCure Cluster Excellence, Dept Neurophysiol, Berlin, Germany

[7] Max Delbruck Ctr Mol Med, Transgen Core Facil, Robert Rossle Str 10, Berlin, Germany

[8] Berlin Inst Hlth, Kapelle Ufer 2, Berlin, Germany

来源：

SCIENCE | 2017年 / 357卷 / 6357期

关键词：

PREPULSE INHIBITION; EXON CIRCULARIZATION; NEURONAL ENSEMBLES; EXPRESSION; STARTLE; SCHIZOPHRENIA; PLASTICITY; MICRORNA-7; DISCOVERY; EFFICIENT;

D O I：

10.1126/science.aam8526

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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 Cdr1as 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 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 Cdr1as and miRNAs are important for normal brain function.

引用

页数：7

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