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Data from: Short RNA chaperones promote aggregation-resistant TDP-43 conformers to mitigate neurodegeneration

Shorter, James1

Published Mar 16, 2026 on Dryad. https://doi.org/10.5061/dryad.9s4mw6mx4

Data files

Mar 16, 2026 version files 13.87 MB

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Abstract

This dataset contains the numerical values underlying all main figures (Figs. 1–6) and supplementary figures in Copley et al., "Short RNA chaperones promote aggregation-resistant TDP-43 conformers to mitigate neurodegeneration," published in Science. Data encompass: (1) in vitro TDP-43 aggregation prevention turbidity and sedimentation assay values across wild-type and disease-linked TDP-43 variants with multiple short RNA chaperones, including derived IC50 values, and FUS condensation assay values (Figs. 1, 3, 4; figs. S1, S3, S11, S15–S17); (2) electrophoretic mobility shift assay (EMSA) quantification of RNA binding (Figs. 1, 3, 4; figs. S2, S4, S15, S18); (3) fluorescence-based Clip34 stem-loop remodeling assay values (Fig. 1; fig. S2); (4) hydrogen–deuterium exchange mass spectrometry (HX-MS) processed deuterium uptake values for TDP-43 and TDP-435FL in free and Clip34-bound states (Fig. 2; figs. S4–S10); (5) all-atom molecular dynamics simulation-derived values, including per-residue helicity, radius of gyration, and contact frequencies for TDP-43 with and without the AUG12 RNA chaperone (figs. S11–S14); (6) NMR per-residue chemical shift perturbation and intensity ratio values for TDP-43 RRMs upon binding short RNA chaperones (Fig. 4F; fig. S18I); (7) circular dichroism (CD) spectroscopy values for short RNA G-quadruplex characterization (fig. S17K); (8) quantification of Malat1_start-mediated solubilization of preformed TDP-43 condensates (fig. S19); (9) sedimentation and electron microscopy-derived quantification of TDP-43 aggregate size, area, and density following Malat1_start treatment (fig. S20); (10) quantification of cytoplasmic TDP-43 aggregation in optogenetic HEK293 cell models, including biochemical fractionation (Fig. 5; fig. S21); (11) TDP-43 nuclear/cytoplasmic ratio measurements in iPSC-derived motor neurons from healthy control and C9orf72-ALS patients (Fig. 5; fig. S22); (12) oligonucleotide localization quantification in iPSC-derived motor neurons and mouse spinal cord (fig. S22C; figs. S25B, S25C; fig. S26C); (13) RT-PCR quantification of cryptic splicing (STMN2, KCNQ2) in stressed motor neurons (fig. S23); (14) neuritic RNA granule quantification for TDP-43 and STAU1 puncta (fig. S25); and (15) in vivo mouse data including ChAT+ and NeuN+ neuron counts, TDP-43 puncta size and number, and Sort1 exon 17b splicing ratios following intrathecal Malat1_start treatment (Fig. 6; figs. S26, S27). Data are provided as .csv files for all figures for broad accessibility. Depending on the figure, data are additionally provided as either .xlsx (Excel) or .pzfx (GraphPad Prism) files; the latter include graphs and statistical analyses. Files are organized by figure number. All experimental data were generated using recombinant proteins, cultured human cell lines (HEK293, iPSC-derived motor neurons), or C57BL/6J mice under IACUC-approved protocols; computational data were derived from all-atom molecular dynamics simulations. No restrictions apply to data reuse. These data enable independent verification of statistical analyses and re-analysis of RNA chaperone dose-response relationships.