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

Cell Rep. 2020 Apr 7;31(1):107473. doi: 10.1016/j.celrep.2020.03.037.


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.

Keywords: ribosome; single-particle cryo-EM; translational accuracy; uS19 protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cryoelectron Microscopy / methods
  • Humans
  • Models, Molecular
  • Molecular Conformation
  • Peptide Chain Elongation, Translational / genetics*
  • Peptide Chain Elongation, Translational / physiology
  • Protein Biosynthesis / genetics
  • RNA, Messenger / metabolism
  • Ribosomal Proteins / genetics*
  • Ribosomal Proteins / metabolism
  • Ribosomal Proteins / ultrastructure
  • Ribosomes / metabolism*
  • Ribosomes / ultrastructure


  • RNA, Messenger
  • Ribosomal Proteins
  • ribosomal protein S19