Internal cap-initiated translation for efficient protein production ...
2025年2月19日 · Here we introduce two molecular designs that bolster circular mRNA translation through an internal cap-initiated mechanism. The first consists of a circular mRNA with a covalently attached N7...
CleanCap M6 inhibits decapping of exogenously delivered IVT …
Protein expression of exogenous mRNA is a function of both mRNA half-life and translation efficiency. Considering that translation initiation begins with eukaryotic translation initiation factor 4E (eIF4E) binding to the 5′ cap, 9 we asked whether M6 3′OMe had a direct
Control of the eIF4E activity: structural insights and ... - Springer
2021年9月19日 · The central role of eukaryotic translation initiation factor 4E (eIF4E) in controlling mRNA translation has been clearly assessed in the last decades. eIF4E function is essential for numerous physiological processes, such as protein synthesis, cellular growth and differentiation; dysregulation of its activity has been linked to ageing, cancer ...
Chemical and topological design of multicapped mRNA and …
2024年9月23日 · A dual-capped oligo effectively enhanced eIF4E affinity, reducing the K d from 2,214 ± 139 nM to 1,414 ± 135 nM (Fig. 3d and Extended Data Fig. 3f,j), and such enhanced binding affinity was ...
Interaction of trinucleotide cap analogues with eIF4E. (A ...
To this end, eIF4E protein was titrated with increasing concentrations of cap 0 and cap 1 variants of A-, G-or Ctrinucleotides and fluorescence intensity changes at 337 nm (upon 280 nm excitation...
Nat. Biotechnol. | 戴上启动帽，MIT王潇团队提出LEGO增强翻译能力
2024年11月7日 · 结果表明，双帽寡核苷酸显著增强了eIF4E的亲和力，将解离常数（Kd）从2214 ± 139 nM降低至1414 ± 135 nM。 接下来，作者进行了原位RNA分析，以确认双帽结构确实增强了mRNA的翻译效率。通过配对的STARmap和RIBOmap技术，分别在单细胞水平上检测了总mRNA和核糖体结合的 ...
真核起始因子4E - 维基百科，自由的百科全书
真核起始因子4E（英文：eukaryotic initiation factor 4E，简称“eIF4E”）是一种帽结合蛋白，可以特异性地识别mRNA的5'端的帽子结构，它在真核翻译的起始过程中发挥重要作用。
具有三磷酸链修饰的三核苷酸帽类似物：作为 mRNA 加帽试剂的合 …
最近的 COVID-19 大流行证明了体外转录 （IVT） mRNA 的巨大治疗潜力，但其生化特性的改进，如细胞稳定性、反应原性和翻译活性，对于基因替代疗法和抗癌免疫疗法的进一步实际应用至关重要。 克服这些限制的策略之一是对独特的 mRNA 5′ 末端结构 5′ 帽进行化学修饰，该结构负责在多个水平上调节翻译。 这可以通过用合成帽类似物引发体外转录反应来实现。 在这项研究中，我们将高效的三核苷酸 IVT 加帽技术与 5' 帽三磷酸桥的几种修改相结合，合成了一系列 16 种新 …
eIF4E 活性的控制：结构见解和药理学意义,Cellular and Molecular …
eIF4E 和真核起始因子 4G (eIF4G) 之间的相互作用对于翻译机器的组装至关重要，这是 mRNA 翻译的初始步骤。 一组特征明确的蛋白质，称为 4E 结合蛋白 (4E-BPs)，通过竞争 eIF4E 表面上的相同结合位点来抑制 eIF4E-eIF4G 相互作用。
Trinucleotide cap analogs with triphosphate chain modifications ...
2024年9月9日 · In this study, we combined a highly efficient trinucleotide IVT capping technology with several modifications of the 5' cap triphosphate bridge to synthesize a series of 16 new cap analogs. We also combined these modifications with epigenetic marks (2'-O-methylation and m6Am) characteristic of mRNA 5'-ends in higher eukaryotes, which was not ...