Mimicry of Canonical Translation Elongation Underlies Alanine Tail Synthesis in RQC

Mol Cell. 2021 Jan 7;81(1):104-114.e6. doi: 10.1016/j.molcel.2020.11.001. Epub 2020 Nov 30.


Aborted translation produces large ribosomal subunits obstructed with tRNA-linked nascent chains, which are substrates of ribosome-associated quality control (RQC). Bacterial RqcH, a widely conserved RQC factor, senses the obstruction and recruits tRNAAla(UGC) to modify nascent-chain C termini with a polyalanine degron. However, how RqcH and its eukaryotic homologs (Rqc2 and NEMF), despite their relatively simple architecture, synthesize such C-terminal tails in the absence of a small ribosomal subunit and mRNA has remained unknown. Here, we present cryoelectron microscopy (cryo-EM) structures of Bacillus subtilis RQC complexes representing different Ala tail synthesis steps. The structures explain how tRNAAla is selected via anticodon reading during recruitment to the A-site and uncover striking hinge-like movements in RqcH leading tRNAAla into a hybrid A/P-state associated with peptidyl-transfer. Finally, we provide structural, biochemical, and molecular genetic evidence identifying the Hsp15 homolog (encoded by rqcP) as a novel RQC component that completes the cycle by stabilizing the P-site tRNA conformation. Ala tailing thus follows mechanistic principles surprisingly similar to canonical translation elongation.

Keywords: Hsp15; RQC; RqcH; RqcP; SsrA; alanine tailing; cryo-EM; ribosome-associated quality control; ribosomes; translation elongation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacillus subtilis / metabolism*
  • Bacillus subtilis / ultrastructure
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Cryoelectron Microscopy
  • Peptide Chain Elongation, Translational*
  • RNA, Bacterial / genetics
  • RNA, Bacterial / metabolism*
  • RNA, Transfer, Ala / genetics
  • RNA, Transfer, Ala / metabolism*


  • Bacterial Proteins
  • RNA, Bacterial
  • RNA, Transfer, Ala