人類40S核糖體成熟最終步驟的結構基礎獲解析
作者：
小柯機器人發布時間：2020/11/22 23:47:51
德國慕尼黑大學Roland Beckmann研究組報導人類40S核糖體成熟最終步驟的結構基礎。2020年11月18日，《自然》雜誌在線發表了這一最新研究成果。
研究人員報導了人類40S亞基前體的五個冷凍電鏡結構，它們描述了40S組裝最終步驟中的組成和構象進展。這些結構解釋了RIOK1在PNO1的置換和解離中的核心作用，這反過來又使核酸內切酶NOB1發生構象變化和激活。此外，研究人員觀察到兩個因子，即包含真核翻譯起始因子1A結構域蛋白（EIF1AD）和富含亮氨酸的重複序列包含蛋白47（LRRC47），它們與RIOK1和中央rRNA螺旋44附近的40S前晚期顆粒結合。最後，功能數據表明EIF1AD為裝配因子回收和18S-E加工所必需。
因此，這些結果能夠詳細了解人類細胞中40S形成的最後步驟，此外，還為人類與模式生物釀酒酵母之間小核糖體亞基形成的主要差異提供了證據。
據了解，真核生物核糖體由小40S和大60S亞基組成，它們以高度協調的方式組裝。200多個因子確保了核糖體RNA的正確修飾、加工和摺疊，以及核糖體蛋白的及時整合。當最終的rRNA前體18S-E在第3位被內切核酸酶NOB13切割時，小亞基的成熟在細胞質中終止。人類40S前體的結構表明，NOB1被其伴侶PNO14保持為非活性狀態。最終的成熟事件都尚未解決，包括決定性rRNA切割步驟中NOB1的激活以及驅動最後生物發生因子解離的機制。
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