Espinar-Marchena Francisco J, Babiano Reyes, Cruz Jesús
Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, and Departamento de Genética, Universidad de Sevilla, E-41013, Seville, Spain.
Microb Cell. 2017 Apr 27;4(5):144-168. doi: 10.15698/mic2017.05.572.
The synthesis of cytoplasmic eukaryotic ribosomes is an extraordinarily energy-demanding cellular activity that occurs progressively from the nucleolus to the cytoplasm. In the nucleolus, precursor rRNAs associate with a myriad of -acting factors and some ribosomal proteins to form pre-ribosomal particles. These factors include snoRNPs, nucleases, ATPases, GTPases, RNA helicases, and a vast list of proteins with no predicted enzymatic activity. Their coordinate activity orchestrates in a spatiotemporal manner the modification and processing of precursor rRNAs, the rearrangement reactions required for the formation of productive RNA folding intermediates, the ordered assembly of the ribosomal proteins, and the export of pre-ribosomal particles to the cytoplasm; thus, providing speed, directionality and accuracy to the overall process of formation of translation-competent ribosomes. Here, we review a particular class of -acting factors known as "placeholders". Placeholder factors temporarily bind selected ribosomal sites until these have achieved a structural context that is appropriate for exchanging the placeholder with another site-specific binding factor. By this strategy, placeholders sterically prevent premature recruitment of subsequently binding factors, premature formation of structures, avoid possible folding traps, and act as molecular clocks that supervise the correct progression of pre-ribosomal particles into functional ribosomal subunits. We summarize the current understanding of those factors that delay the assembly of distinct ribosomal proteins or subsequently bind key sites in pre-ribosomal particles. We also discuss recurrent examples of RNA-protein and protein-protein mimicry between rRNAs and/or factors, which have clear functional implications for the ribosome biogenesis pathway.
细胞质真核核糖体的合成是一项极其耗能的细胞活动，该活动从核仁逐步进行到细胞质。在核仁中，前体rRNA与众多顺式作用因子及一些核糖体蛋白结合，形成前核糖体颗粒。这些因子包括小核仁核糖核蛋白颗粒（snoRNPs）、核酸酶、ATP酶、GTP酶、RNA解旋酶，以及大量无预测酶活性的蛋白质。它们的协同活动以时空方式协调前体rRNA的修饰和加工、形成有活性的RNA折叠中间体所需的重排反应、核糖体蛋白的有序组装，以及前核糖体颗粒向细胞质的输出；从而为有翻译能力的核糖体形成的整个过程提供速度、方向性和准确性。在此，我们综述一类特殊的顺式作用因子，即“占位因子”。占位因子暂时结合选定的核糖体位点，直到这些位点达到适合用另一种位点特异性结合因子替换占位因子的结构背景。通过这种策略，占位因子在空间上阻止后续结合因子的过早募集、结构的过早形成，避免可能的折叠陷阱，并充当分子时钟，监督前核糖体颗粒正确地逐步形成功能性核糖体亚基。我们总结了目前对那些延迟不同核糖体蛋白组装或随后结合前核糖体颗粒中关键位点的因子的理解。我们还讨论了rRNA和/或因子之间RNA-蛋白质和蛋白质-蛋白质模拟的反复出现的例子，这些例子对核糖体生物发生途径具有明确的功能意义。
