RESUMO
Increasing evidence indicates that alternative splicing of human glucocorticoid receptor (GR) transcripts is implicated in the development of glucocorticoid resistance but the underlying mechanism was not well known. Serine/arginine-rich (SR) proteins and heterogeneous nuclear ribonucleoprotein (hnRNP) A1 play an important role in the spliceosome assembly. In this study, we analyzed the effects of different SR proteins and hnRNP A1 on the alternative splicing of GR pre-mRNA in HeLa and 293T cells using a minigene transfection assay. Our results revealed that only SRp40 could induce a GRalpha to GRbeta shift of pre-mRNA splicing in exon 9 in HeLa cells and this effect induced by SRp40 was further confirmed by small interfering RNA study. However, in 293T cells, SRp40 could not induce this shift. These results indicated that SRp40 may influence the alternative splicing of GR pre-mRNA to regulate the ratio of GRalpha to GRbeta, and this effect is cell-dependent.
Assuntos
Processamento Alternativo/fisiologia , Éxons/genética , Proteínas Nucleares/metabolismo , Precursores de RNA/metabolismo , Proteínas de Ligação a RNA/metabolismo , Receptores de Glucocorticoides/genética , Processamento Alternativo/genética , Linhagem Celular , Primers do DNA/genética , Humanos , Precursores de RNA/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Processamento de Serina-Arginina , TransfecçãoRESUMO
Eight-stranded ß-barrel outer membrane proteins can confer bacterial virulence via resistance to host innate defenses. This resistance function of OmpW, which was recently identified as an eight-stranded ß-barrel protein, was investigated in this study. Our results demonstrated that upregulation of OmpW correlated with increased bacterial survival during phagocytosis. Bacterial mutants harboring a deletion of ompW exhibited a significantly increased phagocytosis rate. Both observations suggest that the OmpW protein protects bacteria against host phagocytosis. In addition, expression of ompW is regulated by iron, which implies that the resistance provided by OmpW may be an important factor in iron-related infectious diseases. Furthermore, OmpW has been identified as a protective antigen that protects mice against bacterial infection and is therefore a promising target for vaccine development against infectious diseases.