Gene- and Species-Specific Hox mRNA Translation by Ribosome Expansion Segments

• DOI: 10.1016/j.molcel.2020.10.023
• Publication Date: 2020-11-16T14:53:40Z
• Authors: Kathrin Leppek; Kotaro Fujii; Nick Quade; Teodorus Theo Sus...; Daniel Boehringer; Tea Lenarčič; Shifeng Xue; Naomi R. Genuth; Nenad Ban; Maria Barna
• Keywords: Homeodomain Proteins; 0303 health sciences; Genes, Homeobox; Saccharomyces cerevisiae; 03 medical and health sciences; Gene Expression Regulation; Species Specificity; RNA, Ribosomal; Protein Biosynthesis; Nucleic Acid Conformation; RNA, Messenger; 5' Untranslated Regions; Ribosomes

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.