An evolutionarily conserved long noncoding RNA TUNA controls pluripotency and neural lineage commitment.
Mol Cell
; 53(6): 1005-19, 2014 Mar 20.
Article
em En
| MEDLINE
| ID: mdl-24530304
ABSTRACT
Here, we generated a genome-scale shRNA library targeting long intergenic noncoding RNAs (lincRNAs) in the mouse. We performed an unbiased loss-of-function study in mouse embryonic stem cells (mESCs) and identified 20 lincRNAs involved in the maintenance of pluripotency. Among these, TUNA (Tcl1 Upstream Neuron-Associated lincRNA, or megamind) was required for pluripotency and formed a complex with three RNA-binding proteins (RBPs). The TUNA-RBP complex was detected at the promoters of Nanog, Sox2, and Fgf4, and knockdown of TUNA or the individual RBPs inhibited neural differentiation of mESCs. TUNA showed striking evolutionary conservation of both sequence- and CNS-restricted expression in vertebrates. Accordingly, knockdown of tuna in zebrafish caused impaired locomotor function, and TUNA expression in the brains of Huntington's disease patients was significantly associated with disease grade. Our results suggest that the lincRNA TUNA plays a vital role in pluripotency and neural differentiation of ESCs and is associated with neurological function of adult vertebrates.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peixe-Zebra
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Doença de Huntington
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Regulação da Expressão Gênica no Desenvolvimento
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Células-Tronco Pluripotentes
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RNA Longo não Codificante
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Neurônios
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article