ArticleThe Journal of biological chemistry2014
Aggregation properties of the small nuclear ribonucleoprotein U1-70K in Alzheimer disease.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Meta-Analysis of Gene Expression Changes in the Blood of Patients with Mild Cognitive Impairment and Alzheimer's Disease Dementia.International journal of molecular sciences · 2019Pooled it
- Aβ Aggregates Bind the U1 Spliceosomal Ribonucleoprotein in Alzheimer Disease Brain.bioRxiv : the preprint server for biology · 2026Article
- NADScience advances · 2025Article
- Making tau amyloid models in vitro: a crucial and underestimated challenge.FEBS letters · 2025Review
- Spliceosome protein alterations differentiate hubs of the default mode connectome during the progression of Alzheimer's disease.Brain pathology (Zurich, Switzerland) · 2025Article
- Protein aggregation identified in olfactory neuronal cells is associated with cognitive impairments in a subset of living schizophrenia patients.Molecular psychiatry · 2025Article
- U1-70K and U1A and tau pathogenesis in demented and non-demented individuals with Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- HAPLN2 forms aggregates and promotes microglial inflammation during brain aging in mice.PLoS biology · 2025Article
- Effects of the therapeutic correction of U1 snRNP complex on Alzheimer's disease.Scientific reports · 2024Article
- Heparin-enriched plasma proteome is significantly altered in Alzheimer's disease.Molecular neurodegeneration · 2024Article
- Expression and Purification of Human U1-70K (snRNP70) and its BAD Domains Using an E. coli Expression System.Current protocols · 2024Article
- Identification of key mRNAs and signaling pathways in obsessive compulsive disorder based on weighted gene co-expression network analysis and cytoHubba plugin.Brain and behavior · 2024Article
- Liquid-liquid phase separation in Alzheimer's disease.Journal of molecular medicine (Berlin, Germany) · 2024Review
- Article
- Oligomeric, phosphorylated, and truncated tau and spliceosome pathology within the entorhinal-hippocampal connectome across stages of Alzheimer's disease.The Journal of comparative neurology · 2023Article
- Moving beyond amyloid and tau to capture the biological heterogeneity of Alzheimer's disease.Trends in neurosciences · 2023Review
- Alzheimer's disease-associated U1 snRNP splicing dysfunction causes neuronal hyperexcitability and cognitive impairment.Nature aging · 2022Article
- Evidence of Filamin A loss of solubility at the prodromal stage of neuropathologically-defined Alzheimer's disease.Frontiers in aging neuroscience · 2022Article
- Brain Cell Type-Specific Nuclear Proteomics Is Imperative to Resolve Neurodegenerative Disease Mechanisms.Frontiers in neuroscience · 2022Review
- Tau Protein Interaction Partners and Their Roles in Alzheimer's Disease and Other Tauopathies.International journal of molecular sciences · 2021Review
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Recent evidence indicates that U1-70K and other U1 small nuclear ribonucleoproteins are Sarkosyl-insoluble and associate with Tau neurofibrillary tangles selectively in Alzheimer disease (AD). Currently, the mechanisms underlying the conversion of soluble nuclear U1 small nuclear ribonucleoproteins into insoluble cytoplasmic aggregates remain elusive. Based on the biochemical and subcellular distribution properties of U1-70K in AD, we hypothesized that aggregated U1-70K itself or other biopolymers (e.g. proteins or nucleic acids) interact with and sequester natively folded soluble U1-70K into insoluble aggregates. Here, we demonstrate that total homogenates from AD brain induce soluble U1-70K from control brain or recombinant U1-70K to become Sarkosyl-insoluble. This effect was not dependent on RNA and did not correlate with detergent-insoluble Tau levels as AD homogenates with reduced levels of these components were still capable of inducing U1-70K aggregation. In contrast, proteinase K-treated AD homogenates and Sarkosyl-soluble AD fractions were unable to induce U1-70K aggregation, indicating that aggregated proteins in AD brain are responsible for inducing soluble U1-70K aggregation. It was determined that the C terminus of U1-70K, which harbors two disordered low complexity (LC) domains, is necessary for U1-70K aggregation. Moreover, both LC1 and LC2 domains were sufficient for aggregation. Finally, protein cross-linking and mass spectrometry studies demonstrated that a U1-70K fragment harboring the LC1 domain directly interacts with aggregated U1-70K in AD brain. Our results support a hypothesis that aberrant forms of U1-70K in AD can directly sequester soluble forms of U1-70K into insoluble aggregates.
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