小柯机器人

美国圣犹大儿童研究医院Scott C. Blanchard研究团队发现，人类的mRNA解码在动力学和结构上与细菌不同。这一研究成果于2023年4月5日在线发表在国际学术期刊《自然》上。

研究人员结合单分子成像和冷冻电镜方法来研究了人类核糖体保真度的分子基础，并揭示解码机制在动力学和结构上都与细菌的不同。尽管在这两个物种中解码是全局性的，但在人类核糖体上，氨基酸-tRNA移动的反应坐标被改变，这个过程慢了一个数量级。这些区别来自于人类核糖体和延伸因子eukaryotic elongation factor 1A（eEF1A）中的真核生物特有的结构元件，它们共同协调了每个mRNA密码子上忠实的tRNA整合。核糖体和eEF1A内构象变化的不同性质和时间解释了真核生物物种中解码保真度的提高是如何实现和潜在调节的。

据介绍，在所有物种中，核糖体通过使用氨基酸-tRNA底物忠实地解码信使RNA（mRNA）的核苷酸序列来合成蛋白质。目前对解码机制的了解主要来自于对细菌系统的研究。虽然关键特征在整个演化过程中是保守的，但真核生物实现了比细菌更高保真度的mRNA解码。在人类中，解码保真度的变化与老化和疾病有关，并代表了病毒和癌症治疗的潜在干预点。

附：英文原文

Title: mRNA decoding in human is kinetically and structurally distinct from bacteria

Author: Holm, Mikael, Natchiar, S. Kundhavai, Rundlet, Emily J., Myasnikov, Alexander G., Watson, Zoe L., Altman, Roger B., Wang, Hao-Yuan, Taunton, Jack, Blanchard, Scott C.

Issue&Volume: 2023-04-05

Abstract: In all species, ribosomes synthesize proteins by faithfully decoding messenger RNA (mRNA) nucleotide sequences using aminoacyl-tRNA substrates. Current knowledge of the decoding mechanism derives principally from studies on bacterial systems1. Although key features are conserved across evolution2, eukaryotes achieve higher-fidelity mRNA decoding than bacteria3. In human, changes in decoding fidelity are linked to ageing and disease and represent a potential point of therapeutic intervention in both viral and cancer treatment4,5,6. Here we combine single-molecule imaging and cryogenic electron microscopy methods to examine the molecular basis of human ribosome fidelity to reveal that the decoding mechanism is both kinetically and structurally distinct from that of bacteria. Although decoding is globally analogous in both species, the reaction coordinate of aminoacyl-tRNA movement is altered on the human ribosome and the process is an order of magnitude slower. These distinctions arise from eukaryote-specific structural elements in the human ribosome and in the elongation factor eukaryotic elongation factor 1A (eEF1A) that together coordinate faithful tRNA incorporation at each mRNA codon. The distinct nature and timing of conformational changes within the ribosome and eEF1A rationalize how increased decoding fidelity is achieved and potentially regulated in eukaryotic species.

DOI: 10.1038/s41586-023-05908-w

Source: https://www.nature.com/articles/s41586-023-05908-w

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/
投稿链接：http://www.nature.com/authors/submit_manuscript.html