B BA CDA

Gl pre-mRNA

Gl mRNA

Gl pre-mRNA (% of Norm untreated)

Gl/MUP mRNAs (% of Norm) 100

100

100 39

45

98 100 93 143 107 100 107

MUP mRNA

N or m

T er N or m

T er N or m T er

NMDI 1 Compound 17

Gl+MUP

Probes

B A

0 20 40 60 80 100

NMDI 1 CHX Treatment

35

S incorpor a tion (A rb it ra ry u n it )

NMDI 1

Sodium arsenite G3BP

C

D A

(150bp)

(110bp)

(340bp)

(270bp) (140bp)

(140bp)

GPx1 pre-mRNA

GPx1 mRNA

MUP mRNA

N or m

T er No rm

T er No rm T er

NMDI 1 Compound 17

GPx1 MUP

Probes

GPx1 pre-mRNA (% of Norm untreated)

GPx1/MUP mRNAs (% of Norm) 100

100

100 45

40

80 100 88 86 102 105 100

B

Rluc mRNA

Fluc/Rluc mRNAs (% of MS2)

100 100

53 ±3

Fluc mRNA

NMDI 1 Compound

Rluc +F luc

Probes

MS2 MS2- hU p f1 MS2- hU p f2 MS2- hU p f3X MS2 MS2- hU p f1 MS2- hU p f2 MS2- hU p f3X

51 ±2 51 ±5 55 ±2 95 ±3 84 ±3

Effector plasmids

( )

NMDI 1

Merge FLAG- hUPF1

hXRN1

Serum

( ) ( )

A

Durand et al. Figure S2 B

(350bp)

(300bp)

NMDI 1

Phospho- hUPF1

CFP- hDCP1a

Merge

NMDI 1 NMDI 1

hSMG5 CFP- hDCP1a

Merge

hSMG6 CFP- hDCP1a

Merge

hSMG7 CFP- hDCP1a

Merge

NMDI 1

Merge YFP- hSMG6

Merge YFP- hSMG7

Merge GPx1- Ter FLAG- hUPF1

Merge GFP- hCCR4

Merge hUPF3-

FLAG

Merge GFP-

GE1 GPx1-

Ter

GPx1- Ter

GPx1- Ter

GPx1- Ter

GPx1- Ter

NMDI 1 NMDI 1 NMDI 1

NMDI 1 NMDI 1 NMDI 1

Durand et al. Figure S4

13

15

17

N N N

N N

N N N

N N

O

N

N N

N

N-(5,6-Dimethyl-5H-pyrido[3',4':4,5]

pyrrolo[2,3-g]isoquinolin-10-yl)- N'-ethyl-propane-1,3-diamine

N'-(5,6-Dimethyl-5H-pyrido[3',4':4,5]

pyrrolo[2,3-g]isoquinolin-10-yl)- N,N-diethyl-propane-1,3-diamine

1-(3-Diethylamino-propylamino)- 5-methyl-6H-pyrido[4,3-b]carbazol-9-ol

29

35

N

Cl

N

N

N

N N

N O

10-Chloro-2,6-dimethyl-2H-pyrido [3‘,4':4,5]pyrrolo[2,3-g]isoquinoline

1-(3-Dimethylamino-propylamino)- 5-methyl-6H-pyrido[4,3-b]carbazol-9-ol

37

N N N

N N

N'-(5,6-Dimethyl-5H-pyrido[3',4':4,5]

pyrrolo[2,3-g]isoquinolin-10-yl)- N,N-dimethyl-propane-1,3-diamine

39

70

81

O

N

N N N

N N

N Cl

H

N

N N O

H

H

Allyl-(9-methoxy-5,11-dimethyl-6H- pyrido[4,3-b]carbazol-1-yl)-amine N,N-Diethyl-N'-(9-methoxy-5,6-dimethyl- 6H-pyrido[4,3-b]carbazol-1-yl)-

ethane-1,2-diamine

6-Chloro-5,10-dimethyl-11H-pyrido [3',2':4,5]pyrrolo[3,2-g]isoquinoline