Distinct types of translation termination generate substrates for ribosome-associated quality control

Natalia Shcherbik, Tatiana A. Chernova, Yury O. Chernoff, Dimitri G. Pestov

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Cotranslational degradation of polypeptide nascent chains plays a critical role in quality control of protein synthesis and the rescue of stalled ribosomes. In eukaryotes, ribosome stalling triggers release of 60S subunits with attached nascent polypeptides, which undergo ubiquitination by the E3 ligase Ltn1 and proteasomal degradation facilitated by the ATPase Cdc48. However, the identity of factors acting upstream in this process is less clear. Here, we examined how the canonical release factors Sup45-Sup35 (eRF1-eRF3) and their paralogs Dom34-Hbs1 affect the total population of ubiquitinated nascent chains associated with yeast ribosomes. We found that the availability of the functional release factor complex Sup45-Sup35 strongly influences the amount of ubiquitinated polypeptides associated with 60S ribosomal subunits, while Dom34-Hbs1 generate 60S-associated peptidyl-tRNAs that constitute a relatively minor fraction of Ltn1 substrates. These results uncover two separate pathways that target nascent polypeptides for Ltn1-Cdc48-mediated degradation and suggest that in addition to canonical termination on stop codons, eukaryotic release factors contribute to cotranslational protein quality control.

Original languageEnglish (US)
Pages (from-to)6840-6852
Number of pages13
JournalNucleic acids research
Volume44
Issue number14
DOIs
StatePublished - Aug 19 2016

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Ribosomes
Quality Control
Peptides
Eukaryotic Large Ribosome Subunits
Ubiquitin-Protein Ligases
Terminator Codon
Ubiquitination
Eukaryota
Adenosine Triphosphatases
Proteins
Yeasts
Population

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

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Distinct types of translation termination generate substrates for ribosome-associated quality control. / Shcherbik, Natalia; Chernova, Tatiana A.; Chernoff, Yury O.; Pestov, Dimitri G.

In: Nucleic acids research, Vol. 44, No. 14, 19.08.2016, p. 6840-6852.

Research output: Contribution to journalArticle

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