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Oncol Lett. 2017 Mar;13(3):1944-1948. doi: 10.3892/ol.2017.5627. Epub 2017 Jan 19.

Effects of PTCs on nonsense-mediated mRNA decay are dependent on PTC location.

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1
School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea.

Abstract

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 in vitro and tumor metastasis in vivo. 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.

KEYWORDS:

nonsense-mediated mRNA decay; pre-mRNA splicing; récepteur d'origine nantais proto-oncogene; stop-codon

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