A regulated PNUTS mRNA to lncRNA splice switch mediates EMT and tumour progression.
Nat Cell Biol
; 19(9): 1105-1115, 2017 Sep.
Article
em En
| MEDLINE
| ID: mdl-28825698
ABSTRACT
The contribution of lncRNAs to tumour progression and the regulatory mechanisms driving their expression are areas of intense investigation. Here, we characterize the binding of heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) to a nucleic acid structural element located in exon 12 of PNUTS (also known as PPP1R10) pre-RNA that regulates its alternative splicing. HnRNP E1 release from this structural element, following its silencing, nucleocytoplasmic translocation or in response to TGFß, allows alternative splicing and generates a non-coding isoform of PNUTS. Functionally the lncRNA-PNUTS serves as a competitive sponge for miR-205 during epithelial-mesenchymal transition (EMT). In mesenchymal breast tumour cells and in breast tumour samples, the expression of lncRNA-PNUTS is elevated and correlates with levels of ZEB mRNAs. Thus, PNUTS is a bifunctional RNA encoding both PNUTS mRNA and lncRNA-PNUTS, each eliciting distinct biological functions. While PNUTS mRNA is ubiquitously expressed, lncRNA-PNUTS appears to be tightly regulated dependent on the status of hnRNP E1 and tumour context.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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RNA Mensageiro
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Proteínas Nucleares
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Precursores de RNA
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Proteínas de Ligação a RNA
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Processamento Alternativo
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Proteínas de Ligação a DNA
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Transição Epitelial-Mesenquimal
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RNA Longo não Codificante
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Neoplasias Pulmonares
Idioma:
En
Revista:
Nat Cell Biol
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos