Nascent polypeptides are degraded by the proteasome concurrently with their synthesis on the ribosome. This process, called cotranslational protein degradation (CTPD), has been observed for years, but the underlying mechanisms remain poorly understood. Equally unclear are the identities of cellular proteins genuinely subjected to CTPD. Here we report the identification of CTPD substrates in the yeast Saccharomyces cerevisiae via a quantitative proteomic analysis. We compared the abundance of individual ribosome-bound nascent chains between a wild type strain and a mutant defective in CTPD. Of 1,422 proteins acquired from the proteomic analysis, 289 species are efficient CTPD substrates, with >30% of their nascent chains degraded cotranslationally. We found that proteins involved in translation, ribosome biogenesis, nuclear transport, and amino acid metabolism are more likely to be targeted for CTPD. There is a strong correlation between CTPD and the translation efficiency. CTPD occurs preferentially to rapidly translated polypeptides. CTPD is also influenced by the protein sequence length; longer polypeptides are more susceptible to CTPD. In addition, proteins with N-terminal disorder have a higher probability of being degraded cotranslationally. Interestingly, the CTPD efficiency is not related to the half-lives of mature proteins. These results for the first time indicate an inverse correlation between CTPD and cotranslational folding on a proteome scale. The implications of this study with respect to the physiological significance of CTPD are discussed.

• PMID: 26961882
• DOI full text
• PMC full text
• PubMed
• PubTator

Reference Type

Journal Article | Research Support, N.I.H., Extramural | Research Support, U.S. Gov't, Non-P.H.S.

Authors

Ha SW, Ju D, Hao W, Xie Y

Primary Lit For

Additional Lit For

Review For