Moon Heegyum, Zheng Xuexiu, Loh Tiing Jen, Jang Ha Na, Liu Yongchao, Jung Da-Woon, Williams Darren R, Shen Haihong
School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea.
Oncol Lett. 2017 Mar;13(3):1944-1948. doi: 10.3892/ol.2017.5627. Epub 2017 Jan 19.
The récepteur d'origine nantais (RON) gene is a proto-oncogene that is responsible for encoding the human macrophage-stimulating protein (MSP) 1 receptor. MSP activation induces RON-mediated cell dissociation, migration and matrix invasion. Isoforms of RON that exclude exons 5 and 6 encode the RONΔ160 protein, which promotes cell transformation and tumor metastasis . Premature termination codons (PTCs) in exons activate the nonsense-mediated mRNA decay (NMD) signaling pathway. The present study demonstrated that PTCs at various locations in the alternative exons 5 and 6 could induce NMD of the majority of the spliced, or partially spliced, isoforms. However, the isoforms that excluded exon 6 or exons 5 and 6 were markedly increased when produced from mutated minigenes with inserted PTCs. Furthermore, the unspliced isoform of intron 5 was not observed to be decreased by the presence of PTCs. Notably, these effects may be dependent on the location of the PTCs. The current study demonstrated a novel mechanism underlying the regulation of NMD in alternative splicing.
源自南特的受体（RON）基因是一种原癌基因，负责编码人巨噬细胞刺激蛋白（MSP）1受体。MSP激活可诱导RON介导的细胞解离、迁移和基质侵袭。缺失外显子5和6的RON异构体编码RONΔ160蛋白，该蛋白可促进细胞转化和肿瘤转移。外显子中的提前终止密码子（PTC）可激活无义介导的mRNA降解（NMD）信号通路。本研究表明，可变外显子5和6中不同位置的PTC可诱导大多数剪接或部分剪接异构体的NMD。然而，当由插入PTC的突变小基因产生时，缺失外显子6或外显子5和6的异构体显著增加。此外，未观察到内含子5的未剪接异构体因PTC的存在而减少。值得注意的是，这些效应可能取决于PTC的位置。当前研究证明了可变剪接中NMD调控的一种新机制。
