RNA sectors and allosteric function within the ribosome

RNA sectors and allosteric function within the ribosome
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核糖体内的 RNA 扇区和变构功能

DOI:
10.1073/pnas.1909634117
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发表时间:
2020
期刊:
Proceedings of the National Academy of Sciences
影响因子:
--
通讯作者:
Schepartz, Alanna
Schepartz, Alanna
中科院分区:
--
文献类型:
--
作者:
Walker, Allison S.;Russ, William P.;Ranganathan, Rama;Schepartz, Alanna

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核糖体将遗传密码翻译成生命所有领域的蛋白质。它的大小和复杂性需要调节核糖体功能的长程相互作用。这些相互作用在很大程度上是未知的。在这里,我们应用一个全球性的协同进化方法,统计耦合分析(SCA),以确定共同进化的23 S核糖体RNA(rRNA)的大亚基内的残基网络(部门)。在蛋白质中,SCA揭示了进化约束的层次组织,在三维结构内形成物理上连续的网络的近乎独立的核苷酸组。使用定量,连续培养与深度测序分析,我们证实,前两个SCA预测部门有助于核糖体功能。这些部门映射到不同的核糖体活动,它们的起源可以追溯到生命所有领域的系统发育分歧。这些发现为绘制核糖体变构图、探索核糖体生物发生和设计核糖体新功能奠定了基础。尽管在化学结构上存在差异,但蛋白质和RNA酶似乎具有共同的相互作用和组装的内部逻辑。
The ribosome translates the genetic code into proteins in all domains of life. Its size and complexity demand long-range interactions that regulate ribosome function. These interactions are largely unknown. Here, we apply a global coevolution method, statistical coupling analysis (SCA), to identify coevolving residue networks (sectors) within the 23S ribosomal RNA (rRNA) of the large ribosomal subunit. As in proteins, SCA reveals a hierarchical organization of evolutionary constraints with near-independent groups of nucleotides forming physically contiguous networks within the three-dimensional structure. Using a quantitative, continuous-culture-with-deep-sequencing assay, we confirm that the top two SCA-predicted sectors contribute to ribosome function. These sectors map to distinct ribosome activities, and their origins trace to phylogenetic divergences across all domains of life. These findings provide a foundation to map ribosome allostery, explore ribosome biogenesis, and engineer ribosomes for new functions. Despite differences in chemical structure, protein and RNA enzymes appear to share a common internal logic of interaction and assembly.
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