Elevations in intracellular glucose concentrations are essential for epithelial cell differentiation by mechanisms that are not fully understood. Glucose has recently been found to directly bind several proteins to alter their functions to enhance differentiation. Among the newly identified glucose-binding proteins is NSUN2, an RNA-binding protein that we identified as indispensable for epidermal differentiation. Glucose was found to bind conserved sequences within NSUN2, enhancing its binding to S-adenosyl-L-methionine and boosting its enzymatic activity. Additionally, glucose enhanced NSUN2’s proximity to proteins involved in mRNA translation, with NSUN2 modulating global messenger RNA (mRNA) translation, particularly that of key pro-differentiation mRNAs containing m5C modifications, such as GRHL3. Glucose thus engages diverse molecular mechanisms beyond its energetic roles to facilitate cellular differentiation processes.

中文翻译：

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葡萄糖结合并激活 NSUN2 以促进翻译和表皮分化


细胞内葡萄糖浓度的升高对于上皮细胞分化至关重要，其机制尚不完全清楚。最近发现葡萄糖直接结合几种蛋白质以改变其功能以增强分化。在新发现的葡萄糖结合蛋白中，NSUN2 是 NSUN2，一种 RNA 结合蛋白，我们确定它是表皮分化所必需的。发现葡萄糖结合 NSUN2 内的保守序列，增强其与 S-腺苷-L-蛋氨酸的结合并增强其酶活性。此外，葡萄糖增强了 NSUN2 与参与 mRNA 翻译的蛋白质的接近性，NSUN2 调节整体信使 RNA （mRNA） 翻译，特别是含有 m5C 修饰的关键促分化 mRNA，例如 GRHL3。因此，葡萄糖在其能量作用之外参与多种分子机制，以促进细胞分化过程。