Interactome analysis reveals that lncRNA HULC promotes aerobic glycolysis through LDHA and PKM2

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). Us...

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Veröffentlicht in:Nature communications 2020-06, Vol.11 (1), p.3162-3162, Article 3162
Hauptverfasser: Wang, Chunqing, Li, Yongmei, Yan, Shuai, Wang, Hao, Shao, Xianfeng, Xiao, Mingming, Yang, Baicai, Qin, Guoxuan, Kong, Ruirui, Chen, Ruibing, Zhang, Ning
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Sprache:eng
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Zusammenfassung: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. Here the authors present a quantitative proteomics strategy to identify long noncoding RNA (lncRNA)-binding proteins and demonstrate its application by characterizing the lncRNA HULC (highly upregulated in liver cancer), which is shown to interact with glycolytic enzymes and modulate their activity.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-020-16966-3