Moon Heegyum, Zheng Xuexiu, Loh Tiing Jen, Jang Ha Na, Liu Yongchao, Jung Da-Woon, Williams Darren R, Shen Haihong
1These authors contributed equally to this manuscript.
School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea.
J Cancer. 2015 Nov 1;6(12):1346-51. doi: 10.7150/jca.13361. eCollection 2015.
RON receptor tyrosine kinase is a proto-oncogene that induces cell migration and matrix invasion. RONΔ160 protein, which is produced by exclusion of exon 5 and 6, promotes cell migration, matrix invasion and protection from apoptosis. Alternative splicing regulation of exon 5 and 6 is not well understood. In this manuscript, we identified several new RNA regulatory elements for alternative splicing of Ron proto-oncogene. Firstly, we demonstrated that RNA sequences from EcoRI cleavage sites regulate alternative splicing of Ron exon 5 and 6. Secondly, we showed that the ~30 nt RNA at upstream end of exon 4 and the ~33 nt RNA at downstream end of exon 7 also modulate splicing of exon 5 and 6. Thirdly, our results indicate that the RNA sequences of the ends in exon 4 and 7 are required for the regulatory functions of the RNA from restriction enzyme cleavage sites. Our results provide a new insight for regulation of alternative splicing of Ron proto-oncogene.
RON受体酪氨酸激酶是一种原癌基因，可诱导细胞迁移和基质侵袭。通过外显子5和6的缺失产生的RONΔ160蛋白可促进细胞迁移、基质侵袭并保护细胞免受凋亡。外显子5和6的可变剪接调控尚未完全明确。在本论文中，我们鉴定了几种新的用于Ron原癌基因可变剪接的RNA调控元件。首先，我们证明来自EcoRI切割位点的RNA序列可调控Ron外显子5和6的可变剪接。其次，我们表明外显子4上游末端约30 nt的RNA和外显子7下游末端约33 nt的RNA也可调节外显子5和6的剪接。第三，我们的结果表明外显子4和7末端的RNA序列对于来自限制酶切割位点的RNA的调控功能是必需的。我们的结果为Ron原癌基因可变剪接的调控提供了新的见解。
