Long noncoding RNA glycoLINC assembles a lower glycolytic complex to promote glycolysis

Non-covalent complexes of glycolytic enzymes termed 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 name glycoLINC (gLINC) acts as a backbone for metabolon formation between all four glycolytic pay-off phase enzymes (PGK1, PGAM1, ENO1 and PKM2) along with 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. This proposes that gLINC makes a functional contribution to cancer cell adaptation and moreover, provides the first example of a lncRNA-facilitated metabolon.糖酵解酶的非共价复合物被称为代谢体（metabolon），这一概念早在20世纪70年代便已被提出，但始终颇具争议。本研究证实，一种受c-Myc调控的长链非编码RNA（long noncoding RNA，lncRNA）被我们命名为glycoLINC（gLINC），其可作为骨架介导糖酵解放能阶段全部四种酶（PGK1、PGAM1、ENO1与PKM2）以及LDHA组装形成代谢体。该gLINC代谢体可增强糖酵解通量、提升ATP生成量，并使细胞在丝氨酸缺乏条件下得以存活。此外，在癌细胞中过表达gLINC，可在饲喂丝氨酸缺乏饲料的小鼠体内促进异种移植瘤生长，这表明癌细胞在代谢重编程过程中会利用gLINC。本研究提出，gLINC对癌细胞的适应性具有功能性贡献，同时还提供了首个由长链非编码RNA介导形成代谢体的实例。