ArticleThe Journal of cell biology2025
NEMF-mediated CAT tailing facilitates translocation-associated quality control.
Article in The Journal of cell biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Ubiquitin and ubiquitin-like modifications in the endoplasmic reticulum stress response.The FEBS journal · 2026Review
- ZOMES: expanding roles of the PCI complexes from protein metabolism to drug discovery.npj metabolic health and disease · 2026Article
- The UFM1 Conjugation System: A Master Regulator of Cellular Stress Surveillance in Human Disease.Biology · 2026Review
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9 authors.
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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.
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