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). 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.
Mesh Terms:
Carrier Proteins, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Glycolysis, Humans, L-Lactate Dehydrogenase, Liver Neoplasms, Proteome, Pyruvate Kinase, RNA, Long Noncoding, Receptor, Fibroblast Growth Factor, Type 1, Transcriptional Activation
Nat Commun
Date: Dec. 22, 2019
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