The translation of messenger RNA (mRNA) is a fundamental process in gene expression, and control of translation is important to regulate protein synthesis in cells. The primary hallmark of eukaryotic mRNAs is their 5′ cap, whose molecular contacts to the eukaryotic translation initiation factor eIF4E govern the initiation of translation. Here we report 5′ cap analogues with photo-cleavable groups (FlashCaps) that prohibit binding to eIF4E and resist cleavage by decapping enzymes. These compounds are compatible with the general and efficient production of mRNAs by in vitro transcription. In FlashCap-mRNAs, the single photocaging group abrogates translation in vitro and in mammalian cells without increasing immunogenicity. Irradiation restores the native cap, triggering efficient translation. FlashCaps overcome the problem of remaining sequence or structure changes in mRNA after irradiation that limited previous designs. Together, these results demonstrate that FlashCaps offer a route to regulate the expression of any given mRNA and to dose mRNA therapeutics with spatio-temporal control.

信使RNA（mRNA）的翻译是基因表达的基本过程，翻译的控制对于调节细胞中的蛋白质合成很重要。真核 mRNA 的主要标志是它们的 5' 帽，其与真核翻译起始因子 eIF4E 的分子接触控制翻译的起始。在这里，我们报告了具有光可切割基团 (FlashCaps) 的 5' 帽类似物，它们禁止与 eIF4E 结合并通过脱帽酶抵抗切割。这些化合物与通过体外转录产生的一般和有效的 mRNA 相容。在 FlashCap-mRNAs 中，单个 photocaging 组在体外和哺乳动物细胞中消除了翻译，而不会增加免疫原性。辐照恢复原生上限，触发高效翻译。FlashCaps 克服了照射后 mRNA 中剩余的序列或结构变化的问题，这限制了以前的设计。总之，这些结果表明 FlashCaps 提供了一种途径来调节任何给定 mRNA 的表达，并通过时空控制来给予 mRNA 治疗剂。