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RRM but not the Asp/Glu domain of hnRNP C1/C2 is required for splicing regulation of Ron exon 11 pre-mRNA

  • Moon, Heegyum (School of Life Sciences, Gwangju Institute of Science and Technology) ;
  • Jang, Ha Na (School of Life Sciences, Gwangju Institute of Science and Technology) ;
  • Liu, Yongchao (School of Life Sciences, Gwangju Institute of Science and Technology) ;
  • Choi, Namjeong (School of Life Sciences, Gwangju Institute of Science and Technology) ;
  • Oh, Jagyeong (School of Life Sciences, Gwangju Institute of Science and Technology) ;
  • Ha, Jiyeon (School of Life Sciences, Gwangju Institute of Science and Technology) ;
  • Kim, Hyeon Ho (Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University) ;
  • Zheng, Xuexiu (School of Life Sciences, Gwangju Institute of Science and Technology) ;
  • Shen, Haihong (School of Life Sciences, Gwangju Institute of Science and Technology)
  • Received : 2019.03.25
  • Accepted : 2019.04.03
  • Published : 2019.11.30

Abstract

The Ron proto-oncogene is a human receptor for macrophage-stimulating protein (MSP). The exclusion of exon 11 in alternative splicing generates ${\Delta}RON$ 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.

Keywords

References

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