Fig. 2: UNC13A and UNC13B are downregulated after TDP-43 knockdown owing to the production of NMD-sensitive transcripts.
From: TDP-43 loss and ALS-risk SNPs drive mis-splicing and depletion of UNC13A
a, Ribosome profiling of TDP-43-knockdown i3Neurons shows a reduction in ribosome occupancy of STMN2, UNC13A and UNC13B transcripts. b, Mass spectrometry-based proteomic analysis shows dose-dependent reduction in protein abundance of UNC13A and TDP-43 upon TDP-43 knockdown in i3Neurons. n = 6 biological replicates. Two-sample t-test. c, Protein and RNA quantification of TDP-43, UNC13A and UNC13B in SH-SY5Y with varying levels of doxycycline-inducible TDP-43 knockdown. n = 3 biological replicates. d, Transcript expression upon treatment with CHX suggests that UNC13A and UNC13B, but not STMN2, are sensitive to NMD. HNRNPL is used as a positive control. n = 7 biological replicates (UNC13A, HNRNPL and STMN2) and 8 biological replicates (UNC13B). One-sample t-test. Data are mean ± s.e.m. (b–d).
