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人类40S核糖体成熟最终步骤的结构基础获解析
2020-11-22 23:47
来源：小柯机器人

德国慕尼黑大学Roland Beckmann研究组报道人类40S核糖体成熟最终步骤的结构基础。2020年11月18日，《自然》杂志在线发表了这一最新研究成果。

研究人员报道了人类40S亚基前体的五个冷冻电镜结构，它们描述了40S组装最终步骤中的组成和构象进展。这些结构解释了RIOK1在PNO1的置换和解离中的核心作用，这反过来又使核酸内切酶NOB1发生构象变化和激活。此外，研究人员观察到两个因子，即包含真核翻译起始因子1A结构域蛋白（EIF1AD）和富含亮氨酸的重复序列包含蛋白47（LRRC47），它们与RIOK1和中央rRNA螺旋44附近的40S前晚期颗粒结合。最后，功能数据表明EIF1AD为装配因子回收和18S-E加工所必需。
 
因此，这些结果能够详细了解人类细胞中40S形成的最后步骤，此外，还为人类与模式生物酿酒酵母之间小核糖体亚基形成的主要差异提供了证据。
 
据了解，真核生物核糖体由小40S和大60S亚基组成，它们以高度协调的方式组装。200多个因子确保了核糖体RNA的正确修饰、加工和折叠，以及核糖体蛋白的及时整合。当最终的rRNA前体18S-E在第3位被内切核酸酶NOB13切割时，小亚基的成熟在细胞质中终止。人类40S前体的结构表明，NOB1被其伴侣PNO14保持为非活性状态。最终的成熟事件都尚未解决，包括决定性rRNA切割步骤中NOB1的激活以及驱动最后生物发生因子解离的机制。
 
附：英文原文

Title: Structural basis for the final steps of human 40S ribosome maturation

Author: Michael Ameismeier, Ivo Zemp, Jasmin van den Heuvel, Matthias Thoms, Otto Berninghausen, Ulrike Kutay, Roland Beckmann

Issue&Volume: 2020-11-18

Abstract: Eukaryotic ribosomes consist of a small 40S and a large 60S subunit that are assembled in a highly coordinated manner. More than 200 factors ensure correct modification, processing and folding of ribosomal RNA and the timely incorporation of ribosomal proteins1,2. Small subunit maturation ends in the cytosol, when the final rRNA precursor, 18S-E, is cleaved at site 3 by the endonuclease NOB13. Previous structures of human 40S precursors have shown that NOB1 is kept in an inactive state by its partner PNO14. The final maturation events, including the activation of NOB1 for the decisive rRNA-cleavage step and the mechanisms driving the dissociation of the last biogenesis factors have, however, remained unresolved. Here we report five cryo-electron microscopy structures of human 40S subunit precursors, which describe the compositional and conformational progression during the final steps of 40S assembly. Our structures explain the central role of RIOK1 in the displacement and dissociation of PNO1, which in turn allows conformational changes and activation of the endonuclease NOB1. In addition, we observe two factors, eukaryotic translation initiation factor 1A domain-containing protein (EIF1AD) and leucine-rich repeat-containing protein 47 (LRRC47), which bind to late pre-40S particles near RIOK1 and the central rRNA helix 44. Finally, functional data shows that EIF1AD is required for efficient assembly factor recycling and 18S-E processing. Our results thus enable a detailed understanding of the last steps in 40S formation in human cells and, in addition, provide evidence for principal differences in small ribosomal subunit formation between humans and the model organism Saccharomyces cerevisiae. Studies of five cryo-electron microscopy structures reveal the composition and conformational progression in the final maturation events of human 40S ribosomal subunit assembly.

DOI: 10.1038/s41586-020-2929-x

Source: https://www.nature.com/articles/s41586-020-2929-x

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


本期文章：《自然》：Online/在线发表

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