Identification of Regulatory-RNAs for Alternative Splicing of Ron Proto-Oncogene

• Published in: Journal of Cancer 2015-01, Vol.6 (12), p.1346-1351
• Main Authors: Moon, Heegyum, Zheng, Xuexiu, Loh, Tiing Jen, Jang, Ha Na, Liu, Yongchao, Jung, Da-Woon, Williams, Darren R, Shen, Haihong
• Format: Article
• Language: English
• Subjects: Short Research Communication
• ISSN: 1837-9664; 1837-9664
• DOI: 10.7150/jca.13361

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.