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Updated: Mar 6, 2026

In Vitro Analysis of E3 Ubiquitin Ligase Function
Published on: May 14, 2021
Global profiling of nascent chain interactors reveals TRIM25 as a co-translational E3 ubiquitin ligase
Wenfeng Xiong1, Zheng Ser2, Radoslaw Mikolaj Sobota2
1Department of Biological Sciences, National University of Singapore, Singapore 117558, Singapore.
Abstract:
Nascent polypeptide chains emerging from the ribosome engage a range of co-translational factors at distinct phases of translation. These co-translational interactions are crucial for proper protein biogenesis and quality control pathways to maintain protein homeostasis. Hence, the systematic identification of these co-translational interactors provides insights into how distinct polypeptide fates are determined. Here, we developed nascent-chain interactor profiling (NCIP), a metabolic-labeling- and chemical-crosslinking-enabled proteomics method to identify proteins interacting with nascent polypeptide chains at a proteome-wide scale. Results from NCIP support the co-translational assembly model of multiple protein complexes and reveal TRIM25 as a co-translational E3 ubiquitin ligase. TRIM25 ubiquitinates misfolded nascent chains for quality control at the ribosome. Our results provide a generalizable framework to systematically profile co-translational interactors.
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