mRNA decoding in human is kinetically and structurally distinct from bacteria.
mRNA decoding in human is kinetically and structurally distinct from bacteria.
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DOI：
10.1038/s41586-023-05908-w
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发表时间：
2023-05
期刊：
影响因子：
64.8
通讯作者：
Blanchard, Scott C.
中科院分区：
文献类型：
--
作者：
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.
在所有物种中，核糖体通过使用氨酰-tRNA底物忠实地解码信使RNA（mRNA）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对细菌系统的研究。虽然关键特征在进化过程中是保守的，但真核生物比细菌实现了更高保真的mRNA解码。在人类中，解码保真度的变化与衰老和疾病有关，并代表了病毒和癌症治疗的潜在治疗干预点。在这里，我们结合联合收割机单分子成像和低温电子显微镜方法来检查人类核糖体保真度的分子基础，揭示解码机制在动力学和结构上都不同于细菌。虽然解码在两个物种中是全局相似的，但氨酰-tRNA运动的反应坐标在人类核糖体上发生了改变，并且该过程慢了一个数量级。这些区别源于人类核糖体和延伸因子真核细胞延伸因子1A（eEF1A）中的真核细胞特异性结构元件，它们共同协调每个mRNA密码子处的忠实tRNA掺入。核糖体和eEF1A内构象变化的不同性质和时间合理化了如何在真核生物中实现和潜在地调节增加的解码保真度。由于人核糖体和延伸因子eEF1A中的真核生物特异性结构元件，人核糖体上氨酰-tRNA运动的反应坐标发生改变，并且该过程与细菌相比慢一个数量级。
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 systems. Although key features are conserved across evolution, eukaryotes achieve higher-fidelity mRNA decoding than bacteria. 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 treatment. 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. The reaction coordinate of aminoacyl-tRNA movement is altered on the human ribosome and the process is an order of magnitude slower compared with bacteria due to eukaryote-specific structural elements in the human ribosome and in the elongation factor eEF1A.
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影响因子：
7.7
作者：
Juette MF;Carelli JD;Rundlet EJ;Brown A;Shao S;Ferguson A;Wasserman MR;Holm M;Taunton J;Blanchard SC
通讯作者：
Blanchard SC
DOI：
10.1107/s2059798318009324
发表时间：
2018-09-01
期刊：
Acta crystallographica. Section D, Structural biology
影响因子：
--
作者：
Afonine PV;Klaholz BP;Moriarty NW;Poon BK;Sobolev OV;Terwilliger TC;Adams PD;Urzhumtsev A
通讯作者：
Urzhumtsev A
影响因子：
16
作者：
Johansson, Magnus;Bouakaz, Elli;Ehrenberg, Mans
通讯作者：
Ehrenberg, Mans
影响因子：
64.5
作者：
Behrmann E;Loerke J;Budkevich TV;Yamamoto K;Schmidt A;Penczek PA;Vos MR;Bürger J;Mielke T;Scheerer P;Spahn CM
通讯作者：
Spahn CM
DOI：
10.1111/j.1432-1033.1977.tb11256.x
发表时间：
1977-01-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
FRESNO, M;JIMENEZ, A;VAZQUEZ, D
通讯作者：
VAZQUEZ, D