Mediator complex regulates alternative mRNA processing via the MED23 subunit.
Mol Cell
; 45(4): 459-69, 2012 Feb 24.
Article
em En
| MEDLINE
| ID: mdl-22264826
ABSTRACT
Mediator complex is an integrative hub for transcriptional regulation. Here we show that Mediator regulates alternative mRNA processing via its MED23 subunit. Combining tandem affinity purification and mass spectrometry, we identified a number of mRNA processing factors that bind to a soluble recombinant Mediator subunit, MED23, but not to several other Mediator components. One of these factors, hnRNP L, specifically interacts with MED23 in vitro and in vivo. Consistently, Mediator partially colocalizes with hnRNP L and the splicing machinery in the cell. Functionally, MED23 regulates a subset of hnRNP L-targeted alternative splicing (AS) and alternative cleavage and polyadenylation (APA) events, as shown by minigene reporters and exon array analysis. ChIP-seq analysis revealed that MED23 can regulate hnRNP L occupancy at their coregulated genes. Taken together, these results demonstrate a crosstalk between Mediator and the splicing machinery, providing a molecular basis for coupling mRNA processing to transcription.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
RNA Mensageiro
/
Processamento Alternativo
/
Complexo Mediador
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Mol Cell
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
China