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Flag-TDP-43WT Flag-TDP-12xQ/N - - TET + + 80 58 46 30 a-Flag a-Tub Suppl. Fig.1

Flag-TDP-43WT (+ TET) Flag-TDP-12xQ/N (+ TET) a-TDP-43 a-HSP70 MERGE (a-TDP-43/a-HSP70 MERGE (a-TDP-43/a-Flag/TOPRO-3 Suppl.Fig. 2

Flag- TDP-12xQ/N Flag- TDP-43WT Flag- TDP-12xQ/N Flag- TDP-43WT Flag-beads Flag-beads beads beads Inputs IP HSP70 a-HSP70 Flag-TDP-12xQ/N 83 a-TDP-43 Flag-TDP-43 47.5 83 endo-TDP-43 a-TDP-43 Suppl.Fig.3

A TDP-12xQ/N DRRM2 TDP-12xQ/N DRRM1 - - + + TET (variant 1) E2 E3 E4 (variant 2) E2 E4 TDP-12xQ/NDRRM1 TDP-12xQ/NDRRM2 (variant 1) (variant 2) a-POLDIP3 B TDP-12xQ/N DRRM1/2, DC TDP-12xQ/N DRRM1/2, DN TDP-12xQ/N DRRM1/2 TDP-12xQ/N DRRM1 TDP-12xQ/N DRRM2 TDP-12xQ/N F4L TDP-12xQ/N TDP-43WT - - - - - - - + - + + + + + + + TET 83 a-Flag 47.5 a-Actin 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Suppl. Fig.4

A NLS NES Q/N TDP-12xQ/N RRM1 RRM2 NES TDP-12xQ/N DN RRM1 RRM2 TDP-12xQ/N DN TDP-12xQ/N B + + TET TDP-12xQ/N DN TDP-12xQ/N TDP-43WT 80 - - - + + + TET (variant 1) a-FLAG E2 E3 E4 (variant 2) E2 E4 RT-PCR C TDP-12xQ/N DN TDP-12xQ/N + + 47.5 TET variant 1 variant 2 a-POLDIP3 Suppl. Fig.5

Flag-TDP-12xQ/N D1/2 DC Flag-TDP-12xQ/N D1/2 DC Flag-TDP-12xQ/N D1/2 DC Flag- TDP-12xQ/N Flag- TDP-12xQ/N Flag- TDP-12xQ/N Flag- TDP-12xQ/N WB: a-Flag Flag-TDP-12xQ/N D1/2 DC Beads Inputs IP: a-Flag endo-TDP-43 WB: a-TDP-43 1 2 3 4 5 6 Suppl. Fig.6

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