{"doi":"10.1083/jcb.202408199","title":"NEMF-mediated CAT tailing facilitates translocation-associated quality control","abstract":"Ribosome stalling during co-translational translocation at the ER causes translocon clogging and impairs ER protein biogenesis. Mammalian cells resolve translocon clogging via a poorly characterized translocation-associated quality control (TAQC) process. Here, we combine a genome-wide CRISPR screen with live-cell imaging to dissect the molecular linchpin of TAQC. We show that TAQC substrates translated from mRNAs bearing a ribosome-stalling poly(A) sequence are degraded by lysosomes and the proteasome. By contrast, the degradation of defective nascent chains encoded by nonstop (NS) mRNAs involves an unconventional ER-associated protein degradation (ERAD) mechanism depending on ER-to-Golgi trafficking, KDEL-mediated substrate retrieval at the Golgi, and a tRNA-binding factor NEMF that appends an aggregation-prone carboxyl tail to stalled NS nascent chains. We propose that NEMF-mediated CAT tailing targets a subset of TAQC substrates via Golgi retrieval for ERAD, safeguarding ER homeostasis.","journal":"The Journal of Cell Biology","year":2025,"id":523138,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9485,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1226348,"name":"Lihui Wang","orcid":"0009-0000-2896-9380","position":1,"is_corresponding":false},{"id":239791,"name":"Yue Xu","orcid":"0000-0002-0958-8846","position":2,"is_corresponding":false},{"id":821857,"name":"Layla Saidi","orcid":null,"position":3,"is_corresponding":false},{"id":1395181,"name":"Xiaorong Wang","orcid":"0009-0007-6700-1277","position":4,"is_corresponding":false},{"id":289624,"name":"Clinton Yu","orcid":"0000-0002-2931-5474","position":5,"is_corresponding":false},{"id":375750,"name":"Sijung Yun","orcid":"0000-0003-1948-3690","position":6,"is_corresponding":false},{"id":289627,"name":"Lan Huang","orcid":"0000-0002-3140-4687","position":7,"is_corresponding":false},{"id":239793,"name":"Yihong Ye","orcid":"0000-0002-9512-7922","position":8,"is_corresponding":false},{"id":1352450,"name":"Amanda Ennis","orcid":null,"position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":null,"created_at":"2026-07-19T02:49:58.707747Z","pmid":"40257401","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}