Gene- and Species-Specific Translation by Ribosome Expansion Segments

Ribosomes have been suggested to directly control gene regulation, however regulatory roles for ribosomal RNA (rRNA) remain largely unexplored. Expansion segments (ESs) consist of a multitude of tentacle-like rRNA structures that extend from the core ribosome in eukaryotes. ESs are remarkably variable in sequence and size across eukaryotic evolution with a largely unknown function. In characterizing ribosome binding to a regulatory element within a Homeobox (Hox) 5’ UTR, we unexpectedly 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 in neural stem cells demonstrates the functional importance for such selective mRNA-rRNA binding in translation control. Together, these studies unravel unexpected gene regulation directly mediated by rRNA.