The potential role of U2AF1L4 cDNA 3’ stretch mutations in oral carcinogenesis

Abstract

Background: U2 small nuclear RNA auxiliary factor 1-like protein 4 (U2AF1L4) plays a crucial role in the physiological alternative splicing of pre-mRNA pools. Material and methods: We analyzed the mutations within U2AF1L4 cDNA 3’ stretch, by Q PCR-Tm calling in cancer and pre-cancer oral biopsies. The conservation of U2AF1L4 across mammals and the binding sites on human U2AF1L4 for carcinogens and therapeutants were scrutinized followed by String mediated protein interactome prediction. Results: In Q PCR-Tm calling, the U2AF1L4 cDNA 3’ stretch showed amplicons with multiple Tm values in diseased (pre-cancer and cancer lesions) cDNA pools varying from the control, indicating mutation in the U2AF1L4 cDNA 3’ stretch oral cancer and pre-cancer lesions of addicted cases. The evolutionary analyses showed that human U2AF1L4 is a highly conserved protein. The molecular docking revealed stable interactions between carcinogens and therapeutants with human U2AF1L4 respectively. The U2AF1L4 interactome comprised of key splice factors like SRSF indicating the plausible broad impact of 3’cDNA mutations in altering the global splicing processes of the oral mucosa. Conclusions: The U2AF1L4 cDNA 3’ stretch comprising exons 6, 7, and 8 imbibes mutations mediated by tobacco, areca nut, and alcohol chronic addiction; playing a crucial role in oral precancer-cancer pathophysiologies.

Keywords

• OSCC
• U2AF1L4
• Q PCR-Tm calling
• Evolution