Abstract
Ron is a human receptor for the macrophage-stimulating protein (MSP). Exon 11 skipping of Ron pre-mRNA produces the RonΔ165 protein that has a deletion of a 49 amino acid region in the β-chain extracellular domain. RonΔ165 is constitutively active even in the absence of its ligand. Through stepwise deletion analysis, we identified a 2-nt RNA enhancer, which is located 74 nt upstream from the 5′ splice site of exon 11, for exon 11 inclusion. Through double-base and single-base substitution analysis of the 2-nt RNA, we demonstrated that the GA, CC, UG and AC dinucleotides on exon 11, in addition to the wild-type AG sequence, function as enhancers for exon 11 inclusion of the Ron pre-mRNA.
Highlights
The RON receptor tyrosine kinase along with c-Sea, c-Met and Stk are members of the MET proto-oncogene family [1]
Through double base and single base substitution analysis on the 2-nt RNA, we demonstrated that the GA, CC, UG and AC dinucleotides on exon 11, in addition to the wild‐type AG sequence, function as enhancers for exon 11 inclusion of Ron pre-mRNA
In order to identify the enhancer on exon 11 for exon 11 inclusion of Ron pre-mRNA, we performed mutagenesis analysis on exon 11
Summary
The RON receptor tyrosine kinase along with c-Sea, c-Met and Stk are members of the MET proto-oncogene family [1]. RON protein is a 180-kDa heterodimeric protein composed of a 40-kDa α chain and a 150-kDa β chain linked by disulfide bonds [3]. While the α chain contains the extracellular domain for ligand binding, the β chain includes the intracellular part that contains a kinase domain and a transmembrane domain [4]. These two chains are derived from the 180-kDa precursor protein by a proteolytic cleavage [5].
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