ArticleNature communications2025
A UFD1 variant encoding a microprotein modulates UFD1f and IPMK ubiquitination to play pivotal roles in anti-stress responses.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- IPMK at the crossroads of cellular signaling in health and disease.FEBS letters · 2026Review
- RNA splicing in health and disease.Molecular biomedicine · 2026Review
- Microproteins in Human Physiology and Pathology.Biochemistry · 2026Review
- [Advances in research on metabolic associated fatty liver disease in 2025].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- Microproteins in Metabolic Biology: Emerging Functions and Potential Roles as Nutrient-Linked Biomarkers.International journal of molecular sciences · 2025Review
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Authors and funding
5 authors.
Funding
Abstract
Eukaryotic cells make multiple efforts to cope with internal and external stresses; such mechanisms include metabolic responses and the generation of stress-responsive mRNA isoforms (SR-mRNAisos), such as the classical XBP1s. Here, we identified a mammalian conserved SR-mRNAiso, UFD1s, which encodes a microprotein with anti-stress functions. UFD1s decreased the K63-linked ubiquitination levels of UFD1 full-length protein (UFD1f) via competitive binding to the E3 ubiquitin ligase MARCH7, and therefore regulated the dynamics of protein ubiquitination. Inositol polyphosphate multikinase (IPMK) was identified as the most significantly UFD1s-regulated target in terms of changes in K48- and K11-ubiquitination. UFD1s promoted autophagy and fatty acid oxidation, and IPMK was consistently destabilized. Ufd1s-deficient male mice exhibited metabolic disorders and accelerated NASH progression. Plasmid or circRNA expressing UFD1s alleviated NASH in mice, indicating that UFD1s has therapeutic value. Our findings revealed a mammalian conserved microprotein that plays crucial roles in anti-stress regulation through the modulation of ubiquitination and metabolism.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.