biostudies-literatureLeBlanc KRBLRD VANIA NIH HHSNINDS NIH HHSNIH HHSugaf032https://www.ebi.ac.uk/biostudies/studies/S-EPMC12469191biostudies-literatureUnknown2(3)Alzheimer's disease (AD) and other tauopathies are neurodegenerative disorders with devastating consequences for cognition and memory. Pathogenic accumulation of tau can be modeled in <i>Caenorhabditis elegans</i>, which recapitulate human neurodegeneration including aging-dependent accumulation of phosphorylated tau, tau aggregation, neuronal dysfunction, and neuron degeneration. Using forward genetic screens to identify genes modulating tau pathology, we identified a single point mutation in <i>dib-1</i> that ameliorates tau-driven behavioral defects, prevents neurodegeneration, and decreases tau protein levels. The <i>dib-1</i> gene encodes a small, highly conserved protein, known as TXNL4A in humans, and participates in mRNA splicing via the U4/U6.U5 tri-snRNP. Notably, heterozygous loNAR molecular medicineTri-snRNP activity modulates tauopathy phenotypes.PMC12469191F99 AG088436U19 AG066567I01 BX005762R01 AG084680R01 AG066729T32 AG052354P40 OD010440R01 AG084552R01 NS064131IK6 BX006467P30 AG066509Liachko NFSaxton ADWheeler JMLatimer CSLeBlanc KREck RJKow RLKraemer BCMcMillan PJKeene CDfalseTri-snRNP activity modulates tauopathy phenotypes.Alzheimer's disease (AD) and other tauopathies are neurodegenerative disorders with devastating consequences for cognition and memory. Pathogenic accumulation of tau can be modeled in <i>Caenorhabditis elegans</i>, which recapitulate human neurodegeneration including aging-dependent accumulation of phosphorylated tau, tau aggregation, neuronal dysfunction, and neuron degeneration. Using forward genetic screens to identify genes modulating tau pathology, we identified a single point mutation in <i>dib-1</i> that ameliorates tau-driven behavioral defects, prevents neurodegeneration, and decreases tau protein levels. The <i>dib-1</i> gene encodes a small, highly conserved protein, known as TXNL4A in humans, and participates in mRNA splicing via the U4/U6.U5 tri-snRNP. Notably, heterozygous lo2025-01-01T00:00:00Z2025 Jul2026-05-31T03:09:27.308Z2026-05-31T03:07:19.805ZS-EPMC124691914125628810.1093/narmme/ugaf032