ArticleNucleic acids research2020
Structural basis of the zinc-induced cytoplasmic aggregation of the RNA-binding protein SFPQ.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Engineering a protein homodimer from a heterodimer: A chimeric DBHS protein.Protein science : a publication of the Protein Society · 2026Article
- The gene-regulating proteins NONO and SFPQ assemble into ordered filaments.Communications biology · 2025Article
- Targeting TRIM59 impairs RNA splicing and promotes neuroblastoma differentiation and therapeutic responses.Journal of experimental & clinical cancer research : CR · 2025Article
- An alternative cytoplasmic SFPQ isoform with reduced phase separation potential is up-regulated in ALS.Science advances · 2025Article
- Gene therapy breakthroughs in ALS: a beacon of hope for 20% of ALS patients.Translational neurodegeneration · 2025Review
- FTO suppresses DNA repair by inhibiting PARP1.Nature communications · 2025Article
- Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases.Signal transduction and targeted therapy · 2025Review
- Structural plasticity of the coiled-coil interactions in human SFPQ.Nucleic acids research · 2025Article
- Glycyl-l-histidyl-l-lysine prevents copper- and zinc-induced protein aggregation and central nervous system cell death in vitro.Metallomics : integrated biometal science · 2024Article
- Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- Induced pluripotent stem cell-derived extracellular vesicles overexpressing SFPQ protect retinal Müller cells against hypoxia-induced injury.Cell biology and toxicology · 2023Article
- circ-hnRNPU inhibits NONO-mediated c-Myc transactivation and mRNA stabilization essential for glycosylation and cancer progression.Journal of experimental & clinical cancer research : CR · 2023Article
- Paraspeckles interact with SWI/SNF subunit ARID1B to regulate transcription and splicing.EMBO reports · 2023Article
- The splicing factor proline and glutamine rich promotes the growth of osteosarcoma via the c-Myc signaling pathway.American journal of cancer research · 2023Article
- Familial ALS-associatedOpen biology · 2022Article
- Role of micronutrients in Alzheimer's disease: Review of available evidence.World journal of clinical cases · 2022Review
- Effect of metal ions on Alzheimer's disease.Brain and behavior · 2022Review
- LncRNA-422 suppresses the proliferation and growth of colorectal cancer cells by targeting SFPQ.Clinical and translational medicine · 2022Article
- Regulation of TIA-1 Condensates: ZnFrontiers in molecular biosciences · 2022Article
- Zinc Binds to RRM2 Peptide of TDP-43.International journal of molecular sciences · 2020Article
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SFPQ is a ubiquitous nuclear RNA-binding protein implicated in many aspects of RNA biogenesis. Importantly, nuclear depletion and cytoplasmic accumulation of SFPQ has been linked to neuropathological conditions such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). Here, we describe a molecular mechanism by which SFPQ is mislocalized to the cytoplasm. We report an unexpected discovery of the infinite polymerization of SFPQ that is induced by zinc binding to the protein. The crystal structure of human SFPQ in complex with zinc at 1.94 Å resolution reveals intermolecular interactions between SFPQ molecules that are mediated by zinc. As anticipated from the crystal structure, the application of zinc to primary cortical neurons induced the cytoplasmic accumulation and aggregation of SFPQ. Mutagenesis of the three zinc-coordinating histidine residues resulted in a significant reduction in the zinc-binding affinity of SFPQ in solution and the zinc-induced cytoplasmic aggregation of SFPQ in cultured neurons. Taken together, we propose that dysregulation of zinc availability and/or localization in neuronal cells may represent a mechanism for the imbalance in the nucleocytoplasmic distribution of SFPQ, which is an emerging hallmark of neurodegenerative diseases including AD and ALS.
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