2. Academic Validation
  3. Global profiling of nascent chain interactors reveals TRIM25 as a co-translational E3 ubiquitin ligase

Global profiling of nascent chain interactors reveals TRIM25 as a co-translational E3 ubiquitin ligase

  • Mol Cell. 2026 Mar 19;86(6):1182-1192.e11. doi: 10.1016/j.molcel.2026.02.007.
Wenfeng Xiong 1,  Zheng Ser 2,  Radoslaw Mikolaj Sobota 2,  Zhewang Lin 3
Affiliations

Affiliations

  • 1 Department of Biological Sciences, National University of Singapore, Singapore 117558, Singapore.
  • 2 Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A(∗)STAR), Singapore 138673, Singapore.
  • 3 Department of Biological Sciences, National University of Singapore, Singapore 117558, Singapore. Electronic address: [email protected].
PMID: 41780531 DOI: 10.1016/j.molcel.2026.02.007
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.

Keywords

co-translational E3 ubiquitin ligase; nascent chain interactors; protein quality control.

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