Assembly of ribosomal subunits occurs via parallel pathways, which accelerate the process and render it more robust. Nonetheless, in vitro analyses have also demonstrated that some assembly pathways are dead-ends, presumably due to rRNA misfolding. If and how these non-productive pathways are avoided during assembly in vivo remains unknown. Here we use a combination of biochemical, genetic, proteomic and structural analyses to demonstrate a role for assembly factors in biasing the folding landscape away from non-productive intermediates. By binding Rrp36, Rrp5 is prevented from forming a premature interaction with the platform, which leads to a dead-end intermediate, and a misassembled platform that is functionally defective. The DEAD-box ATPase Has1 separates Rrp5 and Rrp36, allowing Rrp5 to reposition to the platform, thereby promoting ribosome assembly and enabling rRNA processing. Thus, Rrp36 establishes an ATP-dependent regulatory point that ensures correct platform assembly by opening a new folding channel that avoids funnels to misfolding.

中文翻译：

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阻断死端组装途径为 DEAD-box ATPase Has1 创造了一个调节点，并防止平台错误组装

核糖体亚基的组装通过平行途径发生，这会加速该过程并使其更加稳健。尽管如此，体外分析也表明一些组装途径是死胡同，大概是由于 rRNA 错误折叠。在体内组装过程中是否以及如何避免这些非生产性途径仍然未知。在这里，我们结合使用生化、遗传、蛋白质组学和结构分析来证明组装因素在使折叠景观远离非生产性中间体方面的作用。通过结合 Rrp36，可以防止 Rrp5 与平台形成过早的相互作用，这会导致一个死胡同，以及一个功能有缺陷的错误组装的平台。DEAD-box ATPase Has1 将 Rrp5 和 Rrp36 分开，允许 Rrp5 重新定位到平台上，从而促进核糖体组装并使 rRNA 加工成为可能。因此，Rrp36 建立了一个依赖于 ATP 的调节点，通过打开一个新的折叠通道来确保正确的平台组装，避免漏斗错误折叠。