Release of Ubiquitinated and Non-ubiquitinated Nascent Chains from Stalled Mammalian Ribosomal Complexes by ANKZF1 and Ptrh1

Mol Cell. 2018 Oct 18;72(2):286-302.e8. doi: 10.1016/j.molcel.2018.08.022. Epub 2018 Sep 20.


The ribosome-associated quality control (RQC) pathway degrades nascent chains (NCs) arising from interrupted translation. First, recycling factors split stalled ribosomes, yielding NC-tRNA/60S ribosome-nascent chain complexes (60S RNCs). 60S RNCs associate with NEMF, which recruits the E3 ubiquitin ligase Listerin that ubiquitinates NCs. The mechanism of subsequent ribosomal release of Ub-NCs remains obscure. We found that, in non-ubiquitinated 60S RNCs and 80S RNCs formed on non-stop mRNAs, tRNA is not firmly fixed in the P site, which allows peptidyl-tRNA hydrolase Ptrh1 to cleave NC-tRNA, suggesting the existence of a pathway involving release of non-ubiquitinated NCs. Association with NEMF and Listerin and ubiquitination of NCs results in accommodation of NC-tRNA, rendering 60S RNCs resistant to Ptrh1 but susceptible to ANKZF1, which induces specific cleavage in the tRNA acceptor arm, releasing proteasome-degradable Ub-NCs linked to four 3'-terminal tRNA nucleotides. We also found that TCF25, a poorly characterized RQC component, ensures preferential formation of the K48-ubiquitin linkage.

Keywords: ANKZF1; Listerin; NEMF; Ptrh1; TCF25; Vms1; proteasomal degradation; ribosome-associated quality control; ubiquitination.

Publication types

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

MeSH terms

  • Animals
  • Carrier Proteins / metabolism*
  • Cell Line
  • Cell Line, Tumor
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Mammals / metabolism*
  • Protein Biosynthesis / physiology
  • RNA, Transfer / metabolism
  • Ribosome Subunits, Large, Eukaryotic / metabolism*
  • Ribosomes / metabolism*
  • Ubiquitin / metabolism*
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitination / physiology*


  • ANKZF1 protein, human
  • Carrier Proteins
  • Ubiquitin
  • RNA, Transfer
  • Ubiquitin-Protein Ligases