The splicing activator DAZAP1 integrates splicing control into MEK/Erk-regulated cell proliferation and migration.
Nat Commun
; 5: 3078, 2014.
Article
em En
| MEDLINE
| ID: mdl-24452013
ABSTRACT
Alternative splicing of pre-messenger RNA (mRNA) is a critical stage of gene regulation in response to environmental stimuli. Here we show that DAZAP1, an RNA-binding protein involved in mammalian development and spermatogenesis, promotes inclusion of weak exons through specific recognition of diverse cis-elements. The carboxy-terminal proline-rich domain of DAZAP1 interacts with and neutralizes general splicing inhibitors, and is sufficient to activate splicing when recruited to pre-mRNA. This domain is phosphorylated by the MEK/Erk (extracellular signal-regulated protein kinase) pathway and this modification is essential for the splicing regulatory activity and the nuclear/cytoplasmic translocation of DAZAP1. Using mRNA-seq, we identify endogenous splicing events regulated by DAZAP1, many of which are involved in maintaining cell growth. Knockdown or over-expression of DAZAP1 causes a cell proliferation defect. Taken together, these studies reveal a molecular mechanism that integrates splicing control into MEK/Erk-regulated cell proliferation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Movimento Celular
/
Proteínas de Ligação a RNA
/
Processamento Alternativo
/
MAP Quinase Quinase Quinases
/
MAP Quinases Reguladas por Sinal Extracelular
/
Proliferação de Células
Limite:
Humans
Idioma:
En
Revista:
Nat Commun
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos