真核翻译起始因子5A在蛋白质合成中的功能及机制

在蛋白质合成过程中，除核糖体、氨酰 tRNA和mRNA外，还有多种翻译因子参与其中。真核翻译起始因子5A（eukaryotic translation initiation factor 5A, eIF5A）是维持细胞活性必不可少的翻译因子，在进化上高度保守。eIF5A是真核细胞中唯一含有羟腐胺赖氨酸（hypusine）的蛋白质，该翻译后修饰对eIF5A的活性至关重要。1978年，人们首次鉴定出eIF5A，认为它在翻译起始阶段促进第1个肽键的形成。直到2013年才证实它主要在翻译延伸阶段调控含多聚脯氨酸基序蛋白质的翻译。在经过四十多年研究后，人们对eIF5A的功能有了新的认识。近期基于核糖体图谱数据的分析表明，eIF5A能够缓解翻译延伸过程中核糖体在多种基序处的停滞，并不局限于多聚脯氨酸基序，并且它还能够通过促进肽链的释放增强翻译终止。此外，eIF5A还可以通过调控某些蛋白质的翻译，间接影响细胞内的各种生命活动。本文综述了eIF5A的多种翻译后修饰、在蛋白质合成和细胞自噬过程中的调控作用以及与人类疾病的关系，并与细菌及古细菌中的同源蛋白质进行了比较，探讨了该因子在进化中的保守性，以期为相关领域的研究提供一定的理论基础。

Function and Mechanism of Eukaryotic Translation Initiation Factor 5A in Protein Synthesis

In addition to the ribosome, aminoacyl-tRNA, and mRNA, translation factors are also necessary for protein synthesis. The eukaryotic translation initiation factor 5A (eIF5A) is essential for cell viability and well conserved in all three domains during evolution. It is the only protein in eukaryotic cells that contains the unusual amino acid hypusine and the unique post-translational modification of eIF5A is strictly required for its function. eIF5A was identified in 1978 for the first time and was thought to stimulate the formation of the first peptide bond during translation initiation phase. Its involvement in the translation of polyproline-containing protein was not uncovered until 2013. With the research of over 40 years, our understanding of eIF5A function has changed dramatically. Recent ribosome profile data demonstrate that eIF5A works more generally at many ribosome stalled sites, and not limited to polyproline motif. It also enhances translation termination by facilitating peptide release. Moreover, eIF5A also indirectly regulates various cell life activities by controlling the translation of certain proteins. In this review, we provide a summary of the post-translational modification, the regulating effects during protein synthesis and autophagy as well as the relationship between eIF5A and human diseases, and explore the evolutionary conservation of eIF5A by comparing with the bacterial and archaeal orthologs, so as to provide a theoretical basis for the research in related fields.