Cells must coordinate their metabolism and fate trajectories (1, 2), but the underlying mechanisms are only beginning to be discovered. To understand why the glycolytic enzyme enolase 1 (ENO1) binds RNA (3-6), we studied this phenomenon in vitro, in human cells, and during mouse embryonic stem cell differentiation. We find specific cellular RNA ligands that inhibit ENO1's enzymatic activity in vitro. Increasing the concentration of these ligands in cultured cells inhibits glycolysis. We demonstrate that pluripotent stem cells expressing an ENO1 mutant that is hyper-inhibited by RNA are severely impaired in their glycolytic capacity and in endodermal differentiation, whereas cells with an RNA binding-deficient ENO1 mutant display disproportionately high endodermal marker expression. Our findings uncover ENO1 riboregulation as a novel form of metabolic control. They also describe an unprecedented mechanism involved in the regulation of stem cell differentiation.

中文翻译：

---

RNA通过烯醇酶1调节糖酵解和胚胎干细胞分化。

细胞必须协调其新陈代谢和命运轨迹（1、2），但是其潜在机制才刚刚被发现。要了解为什么糖酵解烯醇酶1（ENO1）会结合RNA（3-6），我们在体外，人细胞中以及小鼠胚胎干细胞分化过程中研究了这种现象。我们发现特定的细胞RNA配体在体外抑制ENO1的酶活性。这些配体在培养细胞中的浓度增加会抑制糖酵解。我们证明，多能干细胞表达被RNA高度抑制的ENO1突变体在其糖酵解能力和内胚层分化中受到严重损害，而具有RNA结合缺陷的ENO1突变体的细胞则显示出不成比例的高内胚层标志物表达。我们的发现揭示了ENO1核糖调节是一种新的代谢控制形式。他们还描述了参与干细胞分化调控的前所未有的机制。