Interactome analysis reveals that lncRNA HULC promotes aerobic glycolysis through LDHA and PKM2
Interactome analysis reveals that lncRNA HULC promotes aerobic glycolysis through LDHA and PKM2
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相互作用组分析揭示lncRNA HULC通过LDHA和PKM2促进有氧糖酵解
DOI：
10.1038/s41467-020-16966-3
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发表时间：
2020-06-22
影响因子：
16.6
通讯作者：
Zhang, Ning
中科院分区：
文献类型：
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作者：
Wang, Chunqing;Li, Yongmei;Zhang, Ning
与蛋白质相互作用是长非编码 RNA (lncRNA) 发挥生物反应的重要方式。在这里，我们报告了一种高通量策略，通过结合妥布霉素亲和纯化和质谱分析 (TOBAP-MS) 来表征体内 lncRNA 相互作用蛋白。使用这种方法，我们鉴定了肝癌 (HULC) 中高度上调的 lncRNA 的 140 种候选结合蛋白。有趣的是，HULC 直接与两种糖酵解酶结合，即乳酸脱氢酶 A (LDHA) 和丙酮酸激酶 M2 (PKM2)。机理研究表明，HULC 作为衔接分子发挥作用，增强 LDHA 和 PKM2 与 1 型成纤维细胞生长因子受体 (FGFR1) 的结合，导致这两种酶的磷酸化升高，从而促进糖酵解。这项研究为研究体内lncRNA相互作用组提供了一种便捷的方法，并揭示了HULC通过协调糖酵解酶的酶活性来促进Warburg效应的独特机制。
Interacting with proteins is a crucial way for long noncoding RNAs (lncRNAs) to exert their biological responses. Here we report a high throughput strategy to characterize lncRNA interacting proteins in vivo by combining tobramycin affinity purification and mass spectrometric analysis (TOBAP-MS). Using this method, we identify 140 candidate binding proteins for lncRNA highly upregulated in liver cancer (HULC). Intriguingly, HULC directly binds to two glycolytic enzymes, lactate dehydrogenase A (LDHA) and pyruvate kinase M2 (PKM2). Mechanistic study suggests that HULC functions as an adaptor molecule that enhances the binding of LDHA and PKM2 to fibroblast growth factor receptor type 1 (FGFR1), leading to elevated phosphorylation of these two enzymes and consequently promoting glycolysis. This study provides a convenient method to study lncRNA interactome in vivo and reveals a unique mechanism by which HULC promotes Warburg effect by orchestrating the enzymatic activities of glycolytic enzymes.