ArticleGenes & development2015
ALS mutations in TLS/FUS disrupt target gene expression.
Article in Genes & development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- SSL-VQ: vector-quantized variational autoencoders for semi-supervised prediction of therapeutic targets across diverse diseases.Bioinformatics (Oxford, England) · 2025Article
- Nuclear pore dysfunction and disease: a complex opportunity.Nucleus (Austin, Tex.) · 2024Review
- Article
- The phase separation-dependent FUS interactome reveals nuclear and cytoplasmic function of liquid-liquid phase separation.Nucleic acids research · 2021Article
- FUS/TLS Suppresses Enterovirus Replication and Promotes Antiviral Innate Immune Responses.Journal of virology · 2021Article
- The ALS-Associated FUS (P525L) Variant Does Not Directly Interfere with Microtubule-Dependent Kinesin-1 Motility.International journal of molecular sciences · 2021Article
- Stress granule subtypes: an emerging link to neurodegeneration.Cellular and molecular life sciences : CMLS · 2020Review
- ALS/FTD-associated protein FUS induces mitochondrial dysfunction by preferentially sequestering respiratory chain complex mRNAs.Genes & development · 2020Article
- Druggable Sphingolipid Pathways: Experimental Models and Clinical Opportunities.Advances in experimental medicine and biology · 2020Review
- A Comparison of Low Read Depth QuantSeq 3' Sequencing to Total RNA-Seq in FUS Mutant Mice.Frontiers in genetics · 2020Article
- Inherited and Sporadic Amyotrophic Lateral Sclerosis and Fronto-Temporal Lobar Degenerations arising from Pathological Condensates of Phase Separating Proteins.Human molecular genetics · 2019Review
- Could an Impairment in Local Translation of mRNAs in Glia be Contributing to Pathogenesis in ALS?Frontiers in molecular neuroscience · 2019Review
- The physiological and pathological biophysics of phase separation and gelation of RNA binding proteins in amyotrophic lateral sclerosis and fronto-temporal lobar degeneration.Brain research · 2018Review
- The Role of Post-Translational Modifications on Prion-Like Aggregation and Liquid-Phase Separation of FUS.International journal of molecular sciences · 2018Review
- Importance of Functional Loss of FUS in FTLD/ALS.Frontiers in molecular biosciences · 2018Review
- Properties of LINE-1 proteins and repeat element expression in the context of amyotrophic lateral sclerosis.Mobile DNA · 2018Article
- Yeast as a Model to Unravel Mechanisms Behind FUS Toxicity in Amyotrophic Lateral Sclerosis.Frontiers in molecular neuroscience · 2018Review
- Widespread Translational Remodeling during Human Neuronal Differentiation.Cell reports · 2017Article
- RNA-binding proteins in neurodegeneration: mechanisms in aggregate.Genes & development · 2017Review
- Alternative splicing as a regulator of development and tissue identity.Nature reviews. Molecular cell biology · 2017Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Amyotrophic lateral sclerosis (ALS) is caused by mutations in a number of genes, including the gene encoding the RNA/DNA-binding protein translocated in liposarcoma or fused in sarcoma (TLS/FUS or FUS). Previously, we identified a number of FUS target genes, among them MECP2. To investigate how ALS mutations in FUS might impact target gene expression, we examined the effects of several FUS derivatives harboring ALS mutations, such as R521C (FUS(C)), on MECP2 expression in transfected human U87 cells. Strikingly, FUS(C) and other mutants not only altered MECP2 alternative splicing but also markedly increased mRNA abundance, which we show resulted from sharply elevated stability. Paradoxically, however, MeCP2 protein levels were significantly reduced in cells expressing ALS mutant derivatives. Providing a parsimonious explanation for these results, biochemical fractionation and in vivo localization studies revealed that MECP2 mRNA colocalized with cytoplasmic FUS(C) in insoluble aggregates, which are characteristic of ALS mutant proteins. Together, our results establish that ALS mutations in FUS can strongly impact target gene expression, reflecting a dominant effect of FUS-containing 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.