Fig. 6: FTD risk gene TMEM106B is a TDP-43-regulated APA target.
From: TDP-43 nuclear loss in FTD/ALS causes widespread alternative polyadenylation changes
a, TDP-43 KD lengthened the 3′ UTR of TMEM106B. b, Targeted APA analysis of TMEM106B using RNA-seq from FTD/ALS brain samples, shown in box plots with centerline, median; box limits, upper and lower quartiles; and whiskers, minimum and maximum. c, Level of the long TMEM106B 3′ UTR is substantially increased in the frontal cortices of FTLD–TDP patients (n = 221) compared with controls (n = 53). Data are presented as mean ± s.e.m.; P values were calculated using two-tailed Mann–Whitney test. d, Western blot shows reduced TMEM106B dimer levels after 12-day TDP-43 KD. Quantitation of protein levels (n = 3 per condition) is presented as mean ± s.e.m.; P values were calculated using one-sided Student’s t-test. e, The schematic of the luciferase activity assay for TMEM106B 3′ UTRs. f, The presence of the long TMEM106B 3′ UTR reduces translation efficiency. Dot plots show that the longer TMEM106B 3′ UTR led to lower luciferase activity (left) and higher RNA levels (right). No insert, a dual-luciferase reporter without TMEM106B 3′ UTRs; short, a dual-luciferase reporter with the short TMEM106B 3′ UTR; long, a dual-luciferase reporter with the long TMEM106B 3′ UTR. Data are presented as mean ± s.e.m.; P values were calculated using one-sided Student’s t-test. Panel e created with BioRender.com.