RNA-binding proteins (RBPs) have been relatively overlooked in cancer research despite their contribution to virtually every cancer hallmark. Here, we use RNA interactome capture (RIC) to characterize the melanoma RBPome and uncover novel RBPs involved in melanoma progression. Comparison of RIC profiles of a non-tumoral versus a metastatic cell line revealed prevalent changes in RNA-binding capacities that were not associated with changes in RBP levels. Extensive functional validation of a selected group of 24 RBPs using five different in vitro assays unveiled unanticipated roles of RBPs in melanoma malignancy. As proof-of-principle we focused on PDIA6, an ER-lumen chaperone that displayed a novel RNA-binding activity. We show that PDIA6 is involved in metastatic progression, map its RNA-binding domain, and find that RNA binding is required for PDIA6 tumorigenic properties. These results exemplify how RIC technologies can be harnessed to uncover novel vulnerabilities of cancer cells.

中文翻译：

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黑色素瘤 RBPome 鉴定揭示 PDIA6 是一种参与转移的非常规 RNA 结合蛋白

尽管 RNA 结合蛋白 (RBP) 对几乎所有癌症标志都有贡献，但它们在癌症研究中却相对被忽视。在这里，我们使用 RNA 相互作用组捕获 (RIC) 来表征黑色素瘤 RBPome，并揭示参与黑色素瘤进展的新 RBP。非肿瘤细胞系与转移性细胞系的 RIC 谱比较揭示了与 RBP 水平变化无关的 RNA 结合能力的普遍变化。使用五种不同的体外试验对一组选定的 24 种 RBP 进行广泛的功能验证，揭示了 RBP 在黑色素瘤恶性肿瘤中的意外作用。作为原理证明，我们专注于 PDIA6，这是一种显示出新的 RNA 结合活性的 ER 腔伴侣。我们显示 PDIA6 参与转移进展，绘制其 RNA 结合域，并发现 PDIA6 的致瘤特性需要 RNA 结合。这些结果举例说明了如何利用 RIC 技术来发现癌细胞的新脆弱性。