ArticleProceedings of the National Academy of Sciences of the United States of America2021
TIA1 potentiates tau phase separation and promotes generation of toxic oligomeric tau.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis that pooled it.
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Who cites it
91 citing papers in PubMed, 1 synthesis or guideline pooled it, 149 citations in OpenAlex.
- Brain DNA methylomic analysis of frontotemporal lobar degeneration reveals OTUD4 in shared dysregulated signatures across pathological subtypes.Acta neuropathologica · 2023Pooled it
- MARK4 enhances stress granule formation under oxidative stress and increases tau accumulation.FEBS open bio · 2026Article
- Review
- Tau dysfunction in alzheimer's disease: molecular and cellular mechanisms, genetic modulation, and therapeutic perspectives.Molecular biology reports · 2026Review
- Nuclear dysfunction in aging and neurodegeneration.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Riboregulation: a non-canonical tau function.Molecular neurodegeneration · 2026Review
- FKBP51 inhibition by SAFit2 modulates tau pathology and cognitive deficits in PS19 mice.Alzheimer's research & therapy · 2026Article
- Cell Cycle Dysfunction and Metabolic Alterations Consistent With Pathological Tau in Progressive Supranuclear Palsy Derived Fibroblasts.Molecular neurobiology · 2026Article
- An unrecognized mechanism of neuroprotection by microglial TIA1-mediated stress granules to prevent neuroinflammation and demyelination in experimental autoimmune encephalomyelitis mice through sequestering ApoE mRNA.Journal of neuroinflammation · 2026Article
- The neuroprotective effect of Cucurbitacin B against Aβ and tau toxicities requires functional HDAC6 and stress granule pathways.Biogerontology · 2026Article
- Reduced plasma TIA-1: bridging established pathology and novel biomarker potential.Alzheimer's research & therapy · 2026Article
- Alzheimer's Aβ catalyzes Tau phase separation and aggregation via early nanocluster solubilization.Nature communications · 2026Article
- Article
- Allele-specific splicing modulates protein isoforms and Alzheimer's risk.bioRxiv : the preprint server for biology · 2026Article
- Decoupling phase separation and fibrillization preserves activity of biomolecular condensates.Nature communications · 2026Article
- Implications of virus-induced stress granules in tauopathies.Translational neurodegeneration · 2026Review
- GPCR-Mediated Cell Intelligence: A Potential Mechanism for Survival and Long-Term Health.Current issues in molecular biology · 2026Review
- Tau condensation on DNA mediates microtubule attachment suggesting a mitotic role for centromere-localized tau.Nature communications · 2026Article
- Multi-omic phenotyping of MAPT V337M neurons reveals early changes in axonogenesis and tau phosphorylation.NPJ dementia · 2026Article
- From dynamic condensates to pathological assemblies: the phase behavior of tau andFrontiers in molecular neuroscience · 2026Review
31 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
Tau protein plays an important role in the biology of stress granules and in the stress response of neurons, but the nature of these biochemical interactions is not known. Here we show that the interaction of tau with RNA and the RNA binding protein TIA1 is sufficient to drive phase separation of tau at physiological concentrations, without the requirement for artificial crowding agents such as polyethylene glycol (PEG). We further show that phase separation of tau in the presence of RNA and TIA1 generates abundant tau oligomers. Prior studies indicate that recombinant tau readily forms oligomers and fibrils in vitro in the presence of polyanionic agents, including RNA, but the resulting tau aggregates are not particularly toxic. We discover that tau oligomers generated during copartitioning with TIA1 are significantly more toxic than tau aggregates generated by incubation with RNA alone or phase-separated tau complexes generated by incubation with artificial crowding agents. This pathway identifies a potentially important source for generation of toxic tau oligomers in tau-related neurodegenerative diseases. Our results also reveal a general principle that phase-separated RBP droplets provide a vehicle for coassortment of selected proteins. Tau selectively copartitions with TIA1 under physiological conditions, emphasizing the importance of TIA1 for tau biology. Other RBPs, such as G3BP1, are able to copartition with tau, but this happens only in the presence of crowding agents. This type of selective mixing might provide a basis through which membraneless organelles bring together functionally relevant proteins to promote particular biological activities.
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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.