Rxivist logo

CAT tails drive on- and off-ribosome degradation of stalled polypeptides

By Cole S Sitron, Onn Brandman

Posted 13 Nov 2018
bioRxiv DOI: 10.1101/469296 (published DOI: 10.1038/s41594-019-0230-1)

Stalled translation produces incomplete, ribosome-associated polypeptides that Ribosome-associated Quality Control (RQC) targets for degradation via the ubiquitin ligase Ltn1. During this process, the Rqc2 protein and large ribosomal subunit elongate stalled polypeptides with carboxy-terminal alanine and threonine residues (CAT tails). Failure to degrade CAT-tailed proteins disrupts global protein homeostasis, as CAT-tailed proteins aggregate and sequester chaperones. Why cells employ such a potentially toxic process during RQC is unclear. Here, we developed quantitative techniques to assess how CAT tails affect stalled polypeptide degradation in Saccharomyces cerevisiae. We found that CAT tails improve Ltn1's efficiency in targeting structured polypeptides, which are otherwise poor Ltn1 substrates. If Ltn1 fails, CAT tails undergo a backup route of ubiquitylation off the ribosome, mediated by the ubiquitin ligase Hul5. Thus, CAT tails functionalize the C-termini of stalled polypeptides to drive their degradation on and off the ribosome.

Download data

  • Downloaded 732 times
  • Download rankings, all-time:
    • Site-wide: 17,292 out of 83,965
    • In cell biology: 727 out of 4,269
  • Year to date:
    • Site-wide: 41,297 out of 83,965
  • Since beginning of last month:
    • Site-wide: 48,379 out of 83,965

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


PanLingua

Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News