ArticleEMBO reports2021
The FUS gene is dual-coding with both proteins contributing to FUS-mediated toxicity.
Article in EMBO reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 48 citations in OpenAlex.
- Splicing the narrative: alternative TARDBP splicing and its relation to neurodegeneration in ALS and FTD.The Journal of clinical investigation · 2026Review
- Systematic Detection of Alternative Open Reading Frames (altORFs) in Cancer Driver Genes.Journal of molecular evolution · 2026Article
- Fused in Sarcoma (FUS) promotes renal cell carcinoma progression via the KCMF1/FUS/CENPT axis and activation of the JNK signaling pathway.Journal of translational medicine · 2025Article
- The dual-coding gene SLC35A4 protects against oxidative stress.Protein science : a publication of the Protein Society · 2025Article
- Eukaryotic Microproteins.Annual review of biochemistry · 2025Review
- Non-canonical ORFs-derived protein products in mitochondria: A multifaceted exploration of their functions in health and disease.Protein science : a publication of the Protein Society · 2025Review
- Noncanonical altPIDD1 protein: unveiling the true major translational output of theLife science alliance · 2025Article
- Deciphering the ghost proteome in ovarian cancer cells by deep proteogenomic characterization.Cell death & disease · 2024Article
- Review
- New Insights into Oxidative Stress and Inflammatory Response in Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- Small but mighty: the rise of microprotein biology in neuroscience.Frontiers in molecular neuroscience · 2024Article
- Microproteins-Discovery, structure, and function.Proteomics · 2023Review
- Readthrough isoform of aquaporin-4 (AQP4) as a therapeutic target for Alzheimer's disease and other proteinopathies.Alzheimer's research & therapy · 2023Review
- Unannotated microprotein EMBOW regulates the interactome and chromatin and mitotic functions of WDR5.Cell reports · 2023Article
- Newfound Coding Potential of Transcripts Unveils Missing Members of Human Protein Communities.Genomics, proteomics & bioinformatics · 2023Article
- Article
- A small protein coded within the mitochondrial canonical gene nd4 regulates mitochondrial bioenergetics.BMC biology · 2023Article
- Small open reading frames: a comparative genetics approach to validation.BMC genomics · 2023Article
- Employing non-targeted interactomics approach and subcellular fractionation to increase our understanding of the ghost proteome.iScience · 2023Article
- Re-evaluating the impact of alternative RNA splicing on proteomic diversity.Frontiers in genetics · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Novel functional coding sequences (altORFs) are camouflaged within annotated ones (CDS) in a different reading frame. We show here that an altORF is nested in the FUS CDS, encoding a conserved 170 amino acid protein, altFUS. AltFUS is endogenously expressed in human tissues, notably in the motor cortex and motor neurons. Over-expression of wild-type FUS and/or amyotrophic lateral sclerosis-linked FUS mutants is known to trigger toxic mechanisms in different models. These include inhibition of autophagy, loss of mitochondrial potential and accumulation of cytoplasmic aggregates. We find that altFUS, not FUS, is responsible for the inhibition of autophagy, and pivotal in mitochondrial potential loss and accumulation of cytoplasmic aggregates. Suppression of altFUS expression in a Drosophila model of FUS-related toxicity protects against neurodegeneration. Some mutations found in ALS patients are overlooked because of their synonymous effect on the FUS protein. Yet, we show they exert a deleterious effect causing missense mutations in the overlapping altFUS protein. These findings demonstrate that FUS is a bicistronic gene and suggests that both proteins, FUS and altFUS, cooperate in toxic mechanisms.
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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 OpenQuestion graph.