Abstract

 

Ron proto-oncogene is a human receptor for macrophage-stimulating protein (MSP). Exclusion of exon 11 in alternative splicing generates ą─RON protein that is constitutively activated. Heterogenous ribonuclear protein (hnRNP) C1/C2 protein is one of the most abundant proteins in cells. In this manuscript, we show that both hnRNP C1 and C2, using the approach of reducing or increasing its expression level in cells, promote exon 11 inclusion of Ron pre-mRNA, and that hnRNP C1 and hnRNP C2 function independently but not cooperatively. Moreover, hnRNP C1 stimulates exon 11 splicing through activating intron 10 but not intron 11 splicing. Furthermore, we show that, whereas the RRM domain is required for hnRNP C1 function, Asp/Glu domain is not required. In conclusion, hnRNP C1/C2 promotes exon 11 splicing independently by stimulating intron 10 splicing through RRM but not Asp/Glu domain.