ArticleMolecular biology of the cell2014
FUS is sequestered in nuclear aggregates in ALS patient fibroblasts.
Article in Molecular biology of the cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Human Dermal Fibroblast: A Promising Cellular Model to Study Biological Mechanisms of Major Depression and Antidepressant Drug Response.Current neuropharmacology · 2020Pooled it
- RNA polymerase II phosphorylation dynamics: from molecular mechanisms to human disease.RNA biology · 2026Review
- Histone modification dynamics in brain aging: unlocking therapeutic potential.Cell death & disease · 2026Review
- A solid beta-sheet structure is formed at the surface of FUS droplets during aging.Nature chemical biology · 2024Article
- Histone post-translational modification and heterochromatin alterations in neurodegeneration: revealing novel disease pathways and potential therapeutics.Frontiers in molecular neuroscience · 2024Review
- Causal ALS genes impact the MHC class II antigen presentation pathway.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- mInternational journal of molecular sciences · 2021Article
- ALS-linked FUS mutants affect the localization of U7 snRNP and replication-dependent histone gene expression in human cells.Scientific reports · 2021Article
- Genome instability and loss of protein homeostasis: converging paths to neurodegeneration?Open biology · 2021Review
- Trends in Understanding the Pathological Roles of TDP-43 and FUS Proteins.Advances in experimental medicine and biology · 2021Article
- Modeling cell-autonomous motor neuron phenotypes in ALS using iPSCs.Neurobiology of disease · 2020Review
- Examining the relationship between astrocyte dysfunction and neurodegeneration in ALS using hiPSCs.Neurobiology of disease · 2019Review
- Quantitative proteomics identifies proteins that resist translational repression and become dysregulated in ALS-FUS.Human molecular genetics · 2019Article
- FUS (fused in sarcoma) is a component of the cellular response to topoisomerase I-induced DNA breakage and transcriptional stress.Life science alliance · 2019Article
- Transcription-Dependent Formation of Nuclear Granules Containing FUS and RNA Pol II.Biochemistry · 2018Article
- The hnRNP RALY regulates PRMT1 expression and interacts with the ALS-linked protein FUS: implication for reciprocal cellular localization.Molecular biology of the cell · 2018Article
- Control of CNS functions by RNA-binding proteins in neurological diseases.Current pharmacology reports · 2018Article
- The prionlike domain of FUS is multiphosphorylated following DNA damage without altering nuclear localization.Molecular biology of the cell · 2018Article
- The Role of Post-Translational Modifications on Prion-Like Aggregation and Liquid-Phase Separation of FUS.International journal of molecular sciences · 2018Review
- Neuron-to-Neuron Transfer of FUS in Drosophila Primary Neuronal Culture Is Enhanced by ALS-Associated Mutations.Journal of molecular neuroscience : MN · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations in the RNA-binding protein FUS have been shown to cause the neurodegenerative disease amyotrophic lateral sclerosis (ALS). We investigate whether mutant FUS protein in ALS patient-derived fibroblasts affects normal FUS functions in the nucleus. We investigated fibroblasts from two ALS patients possessing different FUS mutations and a normal control. Fibroblasts from these patients have their nuclear FUS protein trapped in SDS-resistant aggregates. Genome-wide analysis reveals an inappropriate accumulation of Ser-2 phosphorylation on RNA polymerase II (RNA Pol II) near the transcription start sites of 625 genes for ALS patient cells and after small interfering RNA (siRNA) knockdown of FUS in normal fibroblasts. Furthermore, both the presence of mutant FUS protein and siRNA knockdown of wild-type FUS correlate with altered distribution of RNA Pol II within fibroblast nuclei. A loss of FUS function in orchestrating Ser-2 phosphorylation of the CTD of RNA Pol II is detectable in ALS patient-derived fibroblasts expressing mutant FUS protein, even when the FUS protein remains largely nuclear. A likely explanation for this loss of function is the aggregation of FUS protein in nuclei. Thus our results suggest a specific mechanism by which mutant FUS can have biological consequences other than by the formation of cytoplasmic aggregates.
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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.