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

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, 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 labelling and chemical crosslinking enabled proteomics method to identify proteins interacting with nascent polypeptide chains at a proteome-wide scale. Results from NCIP support a widespread mechanism of co-translational assembly of protein complexes and reveal TRIM25 as a novel co-translational E3 ubiquitin ligase. TRIM25 ubiquitinates misfolded nascent polypeptide chains for quality control at the ribosome. Our results provide a generalisable framework to systematically profile nascent polypeptide chains interactors.

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Zhewang Lin

PROVIDER: PXD062019 | JPOST Repository | Thu Mar 19 00:00:00 GMT 2026

REPOSITORIES: jPOST

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			Action	DRS
	20210705_Uniprot_human_reviewed_isoforms.fasta	Fasta
	20230716_Eclipse_VQ_ZS_ZL_HPG_dss_tmt6_R1_F1.raw	Raw
	20230716_Eclipse_VQ_ZS_ZL_HPG_dss_tmt6_R1_F2.raw	Raw
	20230716_Eclipse_VQ_ZS_ZL_HPG_dss_tmt6_R1_F3.raw	Raw
	20230716_Eclipse_VQ_ZS_ZL_HPG_dss_tmt6_R1_F4.raw	Raw

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