rRNA Expansion Segment 7S Increases Translation Accuracy

Pro- and eukaryotic ribosomes contain very similar active centers, but eukaryotic ribosomes have a higher translational accuracy than their prokaryotic counterparts. Also, they have acquired expansions in their proteins and rRNA which could underlie the increased translational fidelity. The Polacek, Leidel and Wilson labs investigated the role of the rRNA expansion segment 7S for translatinal fidelity and found that it is crucial for translational fidelity. The presence of the expansion segment does not alter the structure of the decoding center but seems to change the structural dynamics of the ribosome. Their findings were published "Evolving precision: rRNA expansion segment 7S modulates translation velocity and accuracy in eukaryal ribosomes" in Nucleic Acids Research.

Ribosome-enhanced translational miscoding of the genetic code causes protein dysfunction and loss of cellular fitness. During evolution, open reading frame length increased, necessitating mechanisms for enhanced translation fidelity. Indeed, eukaryal ribosomes are more accurate than bacterial counterparts, despite their virtually identical, conserved active centers. During the evolution of eukaryotic organisms ribosome expansions at the rRNA and protein level occurred, which potentially increases the options for translation regulation and cotranslational events. Here we tested the hypothesis that ribosomal RNA expansions can modulate the core function of the ribosome, faithful protein synthesis. We demonstrate that a short expansion segment present in all eukaryotes' small subunit, ES7S, is crucial for accurate protein synthesis as its presence adjusts codon-specific velocities and guarantees high levels of cognate tRNA selection. Deletion of ES7S in yeast enhances mistranslation and causes protein destabilization and aggregation, dramatically reducing cellular fitness. Removal of ES7S did not alter ribosome architecture but altered the structural dynamics of inter-subunit bridges thus affecting A-tRNA selection. Exchanging the yeast ES7S sequence with the human ES7S increases accuracy whereas shortening causes the opposite effect. Our study demonstrates that ES7S provided eukaryal ribosomes with higher accuracy without perturbing the structurally conserved decoding center.

Read the Publication in Nucleic Acids Research (Open Access)

Website Polacek Lab

Website Leidel Lab

Abstract, figure and title from Rauscher et al (2024) Nucleic Acids Res published under a CC BY-NC 4.0 license.