| RRM but not Asp/Glu domain of hnRNP C1/C2 is required for splicing regulation of Ron exon 11 pre-mRNA |
| Haihong Shen1,*, Heegyum Moon1,2, Ha Na Jang1, Yongchao Liu1, Namjeong Choi1, Jagyeong Oh1, Jiyeon Ha1, Hyeon Ho Kim3, Xuexiu Zheng1 |
1School of life Sciences, Gwangju Institute of Science and Technology,
2New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation,
3Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology |
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Abstract
Ron proto-oncogene is a human receptor for macrophage-stimulating protein (MSP). Exclusion of exon 11 in alternative splicing generates ツ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.
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| Abstract, Accepted Manuscript(in press) [Submitted on March 25, 2019, Accepted on April 3, 2019] |
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