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首页> 美国卫生研究院文献>International Journal of Molecular Sciences >The Origin and Evolution of Release Factors: Implications for Translation Termination Ribosome Rescue and Quality Control Pathways
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The Origin and Evolution of Release Factors: Implications for Translation Termination Ribosome Rescue and Quality Control Pathways

机译：释放因子的起源和演变：对翻译终止核糖体拯救和质量控制途径的影响

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摘要

The evolution of release factors catalyzing the hydrolysis of the final peptidyl-tRNA bond and the release of the polypeptide from the ribosome has been a longstanding paradox. While the components of the translation apparatus are generally well-conserved across extant life, structurally unrelated release factor peptidyl hydrolases (RF-PHs) emerged in the stems of the bacterial and archaeo-eukaryotic lineages. We analyze the diversification of RF-PH domains within the broader evolutionary framework of the translation apparatus. Thus, we reconstruct the possible state of translation termination in the Last Universal Common Ancestor with possible tRNA-like terminators. Further, evolutionary trajectories of the several auxiliary release factors in ribosome quality control (RQC) and rescue pathways point to multiple independent solutions to this problem and frequent transfers between superkingdoms including the recently characterized ArfT, which is more widely distributed across life than previously appreciated. The eukaryotic RQC system was pieced together from components with disparate provenance, which include the long-sought-after Vms1/ANKZF1 RF-PH of bacterial origin. We also uncover an under-appreciated evolutionary driver of innovation in rescue pathways: effectors deployed in biological conflicts that target the ribosome. At least three rescue pathways (centered on the prfH/RFH, baeRF-1, and C12orf65 RF-PH domains), were likely innovated in response to such conflicts.
机译：催化最终肽基-tRNA键水解和多肽从核糖体释放的释放因子的进化一直是一个长期的悖论。尽管翻译设备的组件在整个生命中通常保存良好，但细菌和古生物真核的茎中出现了结构上不相关的释放因子肽基水解酶（RF-PH）。我们在翻译设备的更广泛的进化框架内分析RF-PH域的多样化。因此，我们用可能的tRNA样终止子重建了最后通用祖先中翻译终止的可能状态。此外，核糖体质量控制（RQC）和抢救途径中几种辅助释放因子的进化轨迹指出了该问题的多种独立解决方案以及超级王国之间的频繁转移，包括最近表征的ArfT，其在生命中的分布比以前更广为人知。真核生物RQC系统由来源不同的组件拼凑而成，其中包括细菌来源的Vms1 / ANKZF1 RF-PH。我们还发现了抢救途径创新中未得到充分认识的进化驱动因素：在针对核糖体的生物冲突中部署的效应子。至少有三种救援途径（以prfH / RFH，baeRF-1和C12orf65 RF-PH域为中心）可以应对此类冲突。

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