The long noncoding RNA glycoLINC assembles a lower glycolytic metabolon to promote glycolysis

Non-covalent complexes of glycolytic enzymes, called metabolons, were postulated in the 1970s, but the concept has been controversial. Here we show that a c-Myc-responsive long noncoding RNA (lncRNA) that we call glycoLINC (gLINC) acts as a backbone for metabolon formation between all four glycolytic payoff phase enzymes (PGK1, PGAM1, ENO1, and PKM2) along with lactate dehydrogenase A (LDHA). The gLINC metabolon enhances glycolytic flux, increases ATP production, and enables cell survival under serine deprivation. Furthermore, gLINC overexpression in cancer cells promotes xenograft growth in mice fed a diet deprived of serine, suggesting that cancer cells employ gLINC during metabolic reprogramming. We propose that gLINC makes a functional contribution to cancer cell adaptation and provide the first example of a lncRNA-facilitated metabolon.

Automated summary

This study reveals a novel long noncoding RNA (lncRNA) called gLINC that acts as a backbone for the formation of a metabolon involving glycolytic enzymes and lactate dehydrogenase A. The gLINC metabolon enhances glycolytic flux, ATP production, and cell survival under serine deprivation. Overexpression of gLINC in cancer cells promotes xenograft growth in mice on a serine-deprived diet, suggesting its role in cancer cell adaptation.