Fu Ting, Chan Tracey W, Bahn Jae Hoon, Kim Tae-Hyung, Rowat Amy C, Xiao Xinshu
Molecular, Cellular, and Integrative Physiology Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA.
iScience. 2022 Aug 2;25(8):104836. doi: 10.1016/j.isci.2022.104836. eCollection 2022 Aug 19.
PODXL, a protein that is dysregulated in multiple cancers, plays an important role in promoting cancer metastasis. In this study, we report that RNA editing promotes the inclusion of a alternative exon. The resulting edited PODXL long isoform is more prone to protease digestion and has the strongest effects on reducing cell migration and cisplatin chemoresistance among the three PODXL isoforms (short, unedited long, and edited long isoforms). Importantly, the editing level of the recoding site and the inclusion level of the alternative exon are strongly associated with overall patient survival in Kidney Renal Clear Cell Carcinoma (KIRC). Supported by significant enrichment of exonic RNA editing sites in alternatively spliced exons, we hypothesize that exonic RNA editing sites may enhance proteomic diversity through alternative splicing, in addition to amino acid changes, a previously under-appreciated aspect of RNA editing function.
PODXL是一种在多种癌症中表达失调的蛋白质，在促进癌症转移中起重要作用。在本研究中，我们报告RNA编辑促进了一个可变外显子的包含。由此产生的编辑后的PODXL长异构体更容易被蛋白酶消化，并且在三种PODXL异构体（短、未编辑的长和编辑后的长异构体）中，对减少细胞迁移和顺铂化疗耐药性的影响最强。重要的是，重编码位点的编辑水平和可变外显子的包含水平与肾透明细胞癌（KIRC）患者的总生存期密切相关。在外显子RNA编辑位点在可变剪接外显子中显著富集的支持下，我们假设外显子RNA编辑位点除了氨基酸变化外，还可能通过可变剪接增强蛋白质组多样性，这是RNA编辑功能以前未被充分认识的一个方面。
Zotero 插件
