Ribosomes have been suggested to directly control gene regulation, but regulatory roles for ribosomal RNA (rRNA) remain largely unexplored. Expansion segments (ESs) consist of multitudes of tentacle-like rRNA structures extending from the core ribosome in eukaryotes. ESs are remarkably variable in sequence and size across eukaryotic evolution with largely unknown functions. In characterizing ribosome binding to a regulatory element within a Homeobox (Hox) 5′ UTR, we identify a modular stem-loop within this element that binds to a single ES, ES9S. Engineering chimeric, “humanized” yeast ribosomes for ES9S reveals that an evolutionary change in the sequence of ES9S endows species-specific binding of Hoxa9 mRNA to the ribosome. Genome editing to site-specifically disrupt the Hoxa9-ES9S interaction demonstrates the functional importance for such selective mRNA-rRNA binding in translation control. Together, these studies unravel unexpected gene regulation directly mediated by rRNA and how ribosome evolution drives translation of critical developmental regulators.

核糖体已被建议直接控制基因调控，但核糖体 RNA (rRNA) 的调控作用在很大程度上仍未得到探索。扩展片段 (ES) 由大量从真核生物的核心核糖体延伸的触手状 rRNA 结构组成。ESs 在真核生物进化过程中的序列和大小变化很大，其功能很大程度上未知。在表征核糖体与Homeobox ( Hox ) 5' UTR内的调控元件结合时，我们确定了该元件内的模块化茎环与单个 ES、ES9S 结合。工程嵌合，“人性化”酵母核糖体ES9S表明ES9S序列中的进化改变赋予物种特异性的结合HOXA9mRNA 到核糖体。基因组编辑位点特异性破坏HOXA9 -ES9S互动演示了这种选择性的mRNA，rRNA基因的翻译控制结合功能的重要性。总之，这些研究揭示了由 rRNA 直接介导的意外基因调控以及核糖体进化如何驱动关键发育调节因子的翻译。