Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function.
Science
; 357(6357)2017 09 22.
Article
em En
| MEDLINE
| ID: mdl-28798046
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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RNA
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Processamento Pós-Transcricional do RNA
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MicroRNAs
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RNA Longo não Codificante
Tipo de estudo:
Etiology_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article