Ghalei Homa, Trepreau Juliette, Collins Jason C, Bhaskaran Hari, Strunk Bethany S, Karbstein Katrin
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, Jupiter, FL 33458, USA.
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, Jupiter, FL 33458, USA.
Mol Cell. 2017 Sep 21;67(6):990-1000.e3. doi: 10.1016/j.molcel.2017.08.007. Epub 2017 Sep 7.
Late in their maturation, nascent small (40S) ribosomal subunits bind 60S subunits to produce 80S-like ribosomes. Because of the analogy of this translation-like cycle to actual translation, and because 80S-like ribosomes do not produce any protein, it has been suggested that this represents a quality control mechanism for subunit functionality. Here we use genetic and biochemical experiments to show that the essential ATPase Fap7 promotes formation of the rotated state, a key intermediate in translocation, thereby releasing the essential assembly factor Dim1 from pre-40S subunits. Bypassing this quality control step produces defects in reading frame maintenance. These results show how progress in the maturation cascade is linked to a test for a key functionality of 40S ribosomes: their ability to translocate the mRNA⋅tRNA pair. Furthermore, our data demonstrate for the first time that the translation-like cycle is a quality control mechanism that ensures the fidelity of the cellular ribosome pool.
在其成熟后期，新生的小（40S）核糖体亚基与60S亚基结合形成类似80S的核糖体。由于这种类似翻译的循环与实际翻译相似，并且由于类似80S的核糖体不产生任何蛋白质，有人提出这代表了亚基功能的质量控制机制。在这里，我们使用遗传和生化实验表明，必需的ATP酶Fap7促进旋转状态的形成，这是转位过程中的关键中间体，从而从40S前体亚基中释放必需的组装因子Dim1。绕过这个质量控制步骤会导致阅读框维持出现缺陷。这些结果表明了成熟级联反应的进展如何与对40S核糖体关键功能的测试相关联：它们转运mRNA·tRNA对的能力。此外，我们的数据首次证明类似翻译的循环是一种质量控制机制，可确保细胞核糖体库的保真度。
