A G-tract element in apoptotic agents-induced alternative splicing.
Nucleic Acids Res
; 36(10): 3320-31, 2008 Jun.
Article
em En
| MEDLINE
| ID: mdl-18440980
ABSTRACT
Alternative splicing of a single pre-mRNA transcript can produce protein isoforms that promote either cell growth or death. Here we show that Ro-31-8220 (Ro), an apoptotic agent that inhibits protein kinase C and activates the c-Jun N terminal kinase, decreased the proportion of the cell growth-promoting Bcl-xL splice variant. Targeted mutagenesis analyses narrowed down a critical sequence to a 16-nt G-tract element (Gt16). Transferring this element to a heterologous gene conferred Ro response on an otherwise constitutive exon. The Ro effect was reduced by okadaic acid, an inhibitor of protein phosphatases PP1 and PP2A, in a concentration-dependent manner. Search in the human genome followed by RT-PCR identified a group of genes that contain similar exonic G-tract elements and are responsive to Ro. Moreover, the Gt16 element also mediates the regulation of alternative splicing by other cell apoptosis-inducers particularly retinoic acid. Therefore, the G-tract element likely plays a role in the apoptotic agents-induced alternative splicing of a group of genes. The functions of these genes imply that this regulation will have impact on cell growth/death.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA Mensageiro
/
Precursores de RNA
/
Apoptose
/
Processamento Alternativo
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Sequências Reguladoras de Ácido Ribonucleico
/
Proteína bcl-X
Limite:
Humans
Idioma:
En
Revista:
Nucleic Acids Res
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
China