Alanine Tails Signal Proteolysis in Bacterial Ribosome-Associated Quality Control

Iryna Lytvynenko, Helge Paternoga, Anna Thrun, Annika Balke, Tina A. Müller, Christina H. Chiang, Katja Nagler, George Tsaprailis, Simon Anders, Ilka Bischofs, Julie A. Maupin-Furlow, Christian M.T. Spahn, Claudio A.P. Joazeiro

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

In ribosome-associated quality control (RQC), Rqc2/NEMF closely supports the E3 ligase Ltn1/listerin in promoting ubiquitylation and degradation of aberrant nascent-chains obstructing large (60S) ribosomal subunits—products of ribosome stalling during translation. However, while Ltn1 is eukaryote-specific, Rqc2 homologs are also found in bacteria and archaea; whether prokaryotic Rqc2 has an RQC-related function has remained unknown. Here, we show that, as in eukaryotes, a bacterial Rqc2 homolog (RqcH) recognizes obstructed 50S subunits and promotes nascent-chain proteolysis. Unexpectedly, RqcH marks nascent-chains for degradation in a direct manner, by appending C-terminal poly-alanine tails that act as degrons recognized by the ClpXP protease. Furthermore, RqcH acts redundantly with tmRNA/ssrA and protects cells against translational and environmental stresses. Our results uncover a proteolytic-tagging mechanism with implications toward the function of related modifications in eukaryotes and suggest that RQC was already active in the last universal common ancestor (LUCA) to help cope with incomplete translation. Incompletely synthesized proteins (e.g., the products of ribosome stalling during translation) are potentially toxic and must be eliminated. This is a task for Rqc2/NEMF and Ltn1/listerin in the eukaryotic pathway of ribosome-associated protein quality control. Lytvynenko et al. investigate whether prokaryotic Rqc2 homologs function similarly. Their results suggest that organisms in all domains of life have a related, Rqc2-mediated mechanism that extends the C termini of incomplete nascent-chains with peptide sequences (poly-alanine in bacteria) to promote nascent-chain degradation directly or indirectly.

Original languageEnglish (US)
Pages (from-to)76-90.e22
JournalCell
Volume178
Issue number1
DOIs
StatePublished - Jun 27 2019

Keywords

  • Ala tails
  • CAT tails
  • Ltn1
  • RQC
  • Rqc2
  • RqcH
  • bacterial proteolysis
  • protein quality control
  • ribosome stalling
  • ssrA

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Lytvynenko, I., Paternoga, H., Thrun, A., Balke, A., Müller, T. A., Chiang, C. H., Nagler, K., Tsaprailis, G., Anders, S., Bischofs, I., Maupin-Furlow, J. A., Spahn, C. M. T., & Joazeiro, C. A. P. (2019). Alanine Tails Signal Proteolysis in Bacterial Ribosome-Associated Quality Control. Cell, 178(1), 76-90.e22. https://doi.org/10.1016/j.cell.2019.05.002