RRM but not the Asp/Glu domain of hnRNP C(1)/C(2) is required for splicing regulation of Ron exon 11 pre-mRNA

The Ron proto-oncogene is a human receptor for macrophage-stimulating protein (MSP). The exclusion of exon 11 in alternative splicing generates ΔRON protein that is constitutively activated. Heterogenous ribonucleaoprotein (hnRNP) C(1)/C(2) is one of the most abundant proteins in cells. In this manuscript, we showed that both hnRNP C(1) and C(2) promoted exon 11 inclusion of Ron pre-mRNA and that hnRNP C(1) and hnRNP C(2) functioned independently but not cooperatively. Moreover, hnRNP C(1) stimulated exon 11 splicing through intron 10 activation but not through intron 11 splicing. Furthermore, we showed that, whereas the RRM domain was required for hnRNP C(1) function, the Asp/Glu domain was not. In conclusion, hnRNP C(1)/C(2) promoted exon 11 splicing independently by stimulating intron 10 splicing through RRM but not through the Asp/Glu domain.