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美国斯坦福大学医学院Joseph D. Puglisi研究团队最新研究发现，真核起始因子5B（eIF5B）负责从翻译起始到延伸的过渡。这一研究成果在线发表于2019年9月18日的《自然》。

课题组研究人员使用体外单分子荧光显微镜方法，在纯化酵母酵母翻译系统中以实时直接监测晚期翻译起始和转变为延伸的途径。这种转变在真核生物系统中比大肠杆菌中要慢。延长的缓慢进入由eIF5B在80S核糖体上的一个较长的停留时间所决定，这是在单个核糖体亚单位连接后的一个过程，该过程是由这个普遍保守的起始因子催化的。核糖体亚基连接后对eIF5B GTPase活性的抑制阻止了eIF5B与80S复合物的解离，从而阻止了延伸。研究结果阐明了eIF5B的解离是如何作为从起始到延伸过渡的一个动力学检查点，以及它的释放如何通过引发GTP水解的核糖体复合物构象的变化来控制。

研究人员表示，翻译起始通过建立蛋白质合成的阅读框来决定mRNA中编码的蛋白质的数量和身份。在真核细胞中，许多翻译起始因子为多肽合成准备核糖体，然而，这个过程的基本动态仍然不清楚。因此，一个核心问题是真核核糖体如何从翻译起始过渡到延伸。

附：英文原文

Title: eIF5B gates the transition from translation initiation to elongation

Author: Jinfan Wang, Alex G. Johnson, Christopher P. Lapointe, Junhong Choi, Arjun Prabhakar, Dong-Hua Chen, Alexey N. Petrov, Joseph D. Puglisi

Issue&Volume: 2019-09-18

Abstract: 

Translation initiation determines both the quantity and identity of the protein that is encoded in an mRNA by establishing the reading frame for protein synthesis. In eukaryotic cells, numerous translation initiation factors prepare ribosomes for polypeptide synthesis; however, the underlying dynamics of this process remain unclear1,2. A central question is how eukaryotic ribosomes transition from translation initiation to elongation. Here we use in vitro single-molecule fluorescence microscopy approaches in a purified yeast Saccharomyces cerevisiae translation system to monitor directly, in real time, the pathways of late translation initiation and the transition to elongation. This transition was slower in our eukaryotic system than that reported for Escherichia coli3,4,5. The slow entry to elongation was defined by a long residence time of eukaryotic initiation factor 5B (eIF5B) on the 80S ribosome after the joining of individual ribosomal subunits—a process that is catalysed by this universally conserved initiation factor. Inhibition of the GTPase activity of eIF5B after the joining of ribosomal subunits prevented the dissociation of eIF5B from the 80S complex, thereby preventing elongation. Our findings illustrate how the dissociation of eIF5B serves as a kinetic checkpoint for the transition from initiation to elongation, and how its release may be governed by a change in the conformation of the ribosome complex that triggers GTP hydrolysis.

DOI: 10.1038/s41586-019-1561-0

Source:https://www.nature.com/articles/s41586-019-1561-0

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
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