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

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.