Dynamics of uS19 C-Terminal Tail during the Translation Elongation Cycle in Human Ribosomes

Abstract

Summary: Ribosomes undergo multiple conformational transitions during translation elongation. Here, we report the high-resolution cryoelectron microscopy (cryo-EM) structure of the human 80S ribosome in the post-decoding pre-translocation state (classical-PRE) at 3.3-Å resolution along with the rotated (hybrid-PRE) and the post-translocation states (POST). The classical-PRE state ribosome structure reveals a previously unobserved interaction between the C-terminal region of the conserved ribosomal protein uS19 and the A- and P-site tRNAs and the mRNA in the decoding site. In addition to changes in the inter-subunit bridges, analysis of different ribosomal conformations reveals the dynamic nature of this domain and suggests a role in tRNA accommodation and translocation during elongation. Furthermore, we show that disease-associated mutations in uS19 result in increased frameshifting. Together, this structure-function analysis provides mechanistic insights into the role of the uS19 C-terminal tail in the context of mammalian ribosomes. : In this study, Bhaskar et al. visualize the dynamic rearrangement of the uS19 C-terminal tail during translation elongation and elucidate its role in stabilizing aminoacyl tRNA and decoding interactions and in coordination of peptidyl tRNA movements within the mammalian ribosome during protein synthesis. Keywords: ribosome, uS19 protein, translational accuracy, single-particle cryo-EM