For more than four decades now, I have been studying how genetic information is transformed into protein-based cellular functions. This has included investigations into the mechanisms supporting cellular localization of proteins, disulfide bond formation, quality control of membranes, and translation. I tried to extract new principles and concepts that are universal among living organisms from our observations of Escherichia coli. While I wanted to distill complex phenomena into basic principles, I also tried not to overlook any serendipitous observations. In the first part of this article, I describe personal experiences during my studies of the Sec pathway, which have centered on the SecY translocon. In the second part, I summarize my views of the recent revival of translation studies, which has given rise to the concept that nonuniform polypeptide chain elongation is relevant for the subsequent fates of newly synthesized proteins. Our studies of a class of regulatory nascent polypeptides advance this concept by showing that the dynamic behaviors of the extraribosomal part of the nascent chain affect the ongoing translation process. Vibrant and regulated molecular interactions involving the ribosome, mRNA, and nascent polypeptidyl-tRNA are based, at least partly, on their autonomously interacting properties.

中文翻译：

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漫步新概念

超过四十年来，我一直在研究遗传信息如何转化为基于蛋白质的细胞功能。这包括对支持蛋白质的细胞定位，二硫键形成，膜的质量控制和翻译的机制的研究。我试图从我们对大肠杆菌的观察中提取出在活生物体中普遍存在的新原理和新概念。。虽然我想将复杂的现象提炼为基本原理，但我也尽力不忽视任何偶然的发现。在本文的第一部分中，我描述了我在Sec途径研究中的个人经历，这些经历都集中在SecY易位子上。在第二部分中，我总结了我对近期翻译研究的复兴的观点，该观点引起了这样的观念，即不均匀的多肽链延长与新合成蛋白质的后续命运有关。我们对一类新生多肽的研究通过表明新生链核糖体外部分的动态行为会影响正在进行的翻译过程，从而推动了这一概念的发展。涉及核糖体，mRNA和新生的多肽基-tRNA的充满活力的分子分子相互作用至少部分基于