RPS 12 5 UTR Form B 72 68

RPS 12 (5’ UTR “Form B”) 72 68 76 75 74 73 71 70 69 67 66 65 64 63 62 61 60 59 ES Edited CUAAUACACUUUUGAUAACAAACUAAAGUAAu. AAAuuuu. Guuuu. GCGu. Au. GA*UUUUUGu. Au. G*Guu. Guuu. AC*Guuuu. Auuu. Gu Pre-edited CUAAUACACUUUUGAUAACAAACUAAAGUAA AAA G GCG A G GAUUUUUUG A GUG G G ACUG G A G T-stripped 1 -- ----- +------ ---+ -- ----- + - -- - - +- 58 57 56 55 54 53 52 51 50 49 48 47 46 45 44 43 42 41 40 39 38 37 36 35 45 34 33 uuu. Au. Guu. Au. Au. GAGu. CCG**CGAuu. GCCCAGuu. CCGGu. AACCGACGu. Auu. Gu. Au. GC**C****Gu. Auuuu. Auu. UAu. AAuuuu. GGAu. Gu A G A A A GAG CCGUUCGA GCCCAG CCGG AACCGACG G A GCUUCUUUUG A A UA A AA G GGA G 46 - - + --- --- +------- - - + - -- - +--- - 96 32 31 30 29 28 27 26 25 24 23 22 21 20 19 18 17 16 15 14 13 12 11 u. GCGuu. Guuuu. Auu. GGuuu. AGuu. Au. G**UCAuu. AGA***GGGUGGu. GGuuuu. GAuuu. ACCC***G****Gu. G*UAA GCG G A GG AG A GUUUCA A AGAUUUGGGUGG GG G GA ACCCUUUGUUUUG GUUAA 97 --- + - - --- - +- - - ----+ -- -- ---+- - -- 136 10 9 8 7 6 5 4 3 2 1 AGu. Au. ACA*CG**UAuu. Gu. AAGuu. AGA*UUUAGAu. AUAAGAUAUGUUUUU[AAUA]POLYA AG A A ACAUCGUUUA G AAG AGAUUUUAGA AUAAGAUAUGUUUUU[AAUA]POLYA 137 -- - + --- --+ ----- - --+- - - 163 Fig. S 1

KH 2 F 1 -RNAi Extract RESC 6 -IP A 0 3 4 M 0 3 4 B Tet (days) KREH 2 250 0 3 150 250 100 75 KH 2 F 1 Ig. G 50 37 100 75 75 RESC 2 Ig. G 4 0 3 4 Tet (days) KREH 2 KH 2 F 1 Ig. G RESC 2 Ig. G 50 37 37 2 3 KREL 1 50 4 C 5 KH 2 F 1 -RNAi 105 104 103 102 101 -Tet +Tet 100 0 0 50 100 150 200 250 HOURS KREL 1 50 1 6 D CUMUATIVE GROWTH (MILLIONS) 1 CUMUATIVE GROWTH (MILLIONS) 4 M 0 3 50 37 50 KREH 2 -RNAi Extract KH 2 F 1 -IP RESC 6 -IP 2 3 4 5 6 7 8 9 KREH 2 -RNAi 105 104 103 102 101 -Tet +Tet 100 0 0 50 100 150 200 250 HOURS Fig. S 2

1000 800 ES ++ ++ 50 ++ ++ 70 ++ + ++ 90 + ++ 110 + + 130 Fig. S 3 87643 - + 11 - ++ 181615 - ++ 87643 - 1200 + 11 - 0 + T-str 31 + 181615 - 0 *** * 393735 33323028272624222019 - 31 + mt. RNA KH 2 F 1 -IP RESC 6 -IP 393735 33323028272624222019 - 40 T-str 51 (ES 54) 4846 444341 60 4846 444341 80 50 49 - SITE-BY-SITE EDITS (%) 100 50 49 - B 72 706866 646260585654 535251 - ES 72 706866 646260585654 535251 - CUM. EDITS A TOTAL EDITS * 20 + T-str 51 (ES 54) ++ + 151 3000 2500 600 1500 2000 400 1000 200 500 ++ 151 0

A mt. RNA KREH 2 -IP RESC 6 -IP B CORRECT 128 32 32 16 16 8 8 4 + + + + SITE-BY-SITE EDITS % D INCORRECT 64 + AGG + GAG STOP START C + 151 717273 - + 1087643 - + 11 - + 393735 33323028272624222019 181615 - 7674 72 - ES + 4846 444341 + - 1 17 4 484746 - 2 706866 646260585654 53525150 49 - SITE-BY-SITE EDITS % 100 % 64 CORRECT INCORRECT 8 16 4 4 2 1 1 0. 25 0. 063 0. 016 0. 004 17 + + + + 151 + AGG Fig. S 4 + GAG

ES 2 4 1 0 2 + + 50 + + 70 + + 90 + 110 + + INCOR/COR T-str 80 (ES 46) 3 - 764 - + 3 - + 130 764 - + 8 - 1311 - 1615 - + 8 - + + 18 - + 222019 - mt. RNA KH 2 F 1 -IP RESC 6 -IP 1311 - 3 + 323028272624 - 0. 6 1615 - 4 + 393735 33 - T-str 80 (ES 46) 18 - T-str 48 (ES 57) 4846 444341 50 49 - + 222019 - 5 + 323028272624 - 6 + 393735 33 - 7 T-str 48 (ES 57) 4846 444341 T-str 31 + 50 49 - 0 ** - SITE-BY-SITE EDITS (%) 0. 8 - B 72 706866 646260585654 535251 - ES 31 72 706866 646260585654 535251 - CUM. EDITS A INCOR/COR 0. 4 0. 2 + 151 12 10 8 6 + 151 0 Fig. S 5

-Tet KH 2 F 1 -RNAi +Tet d 3 RESC 6 -IP +Tet d 4 A 64 32 32 16 16 8 4 + AAA + + + START C + 151 STOP D INCORRECT 64 SITE-BY-SITE EDITS (%) + 87643 - 7674 72 - ES + 11 - + 4846 444341 393735 33323028272624222019 181615 - 1 - 17 393837 - 2 706866 646260585654 53525150 49 - SITE-BY-SITE EDITS (%) 100 % B CORRECT 128 16 16 4 1 4 0. 25 2 0. 063 + AAA 0. 016 0. 004 17 + + + + 151 Fig. S 6

CORRECT SITE-BY-SITE EDITS (%) A 64 64 32 32 32 16 16 16 8 8 8 4 4 4 2 2 2 T-str 1 47 48 49 1 79 80 81 82 1 KH 2 F 1 -RNAi RESC 6 -IP 87 88 89 SITE-BY-SITE EDITS (%) INCORRECT T. str RELATIVE TO –TET B -TET (%) 16 8 4 2 1 0. 5 0. 25 0. 12 0. 06 3. 2 47 48 (ES 57) 48 49 16 8 4 2 1 0. 5 0. 25 0. 12 0. 06 3. 2 79 80 81 82 80 (ES 46) 32 16 8 4 2 1 0. 5 0. 25 0. 12 0. 06 FULLY EDITED PRE-EDITED 87 88 3. 2 1. 6 0. 8 0. 4 0. 2 0. 1 0. 05 T-NUMBER 0. 05 1. 0 -TET -Tet +Tet day 3 +Tet day 4 89 88 (ES 39) Fig. S 7

ATPase subunit 6 (A 6) ES 67 66 65 64 63 62 61 60 59 58 57 56 55 54 53 Edited ACGGCGGGAAAuu. Au. CCCAu. UUUUUAuu. GAu. Guuuuuu. GAuuuuuuu. UAuuuuu. Guuuuuu. Au. GGu. Guuuuuu. Guu. Auu. GAuu Pre-edited ACGGCGGGAAA--A-CA-CCCA-UUUUUA--G--GA-G------GA-------UA-----G------A-GG-G------G--A--GA-- + -- -- +- - - -36 T-stripped 1 ----+- - -- ---- 52 51 49 48 50 47 46 45 44 43 42 41 40 39 38 37 36 35 34 33 32 31 u. Auuuuu. Guuuu. Guuu. Auuuu. AUGu. Guuuuu. Au. UUGuu. GGAuuu. Au. UUGCC***GCCAu. Auu. AC****AGuu. Au -A---A-----G-G-----G---A--A----AUG-G-----A-A-UUG--GGA---A-UUGCCUUUGCCA-A--ACUUUUAG--A---A 37 + - -----+-- - --- - 69 29 2827 30 26 25 24 23 22 21 20 19 18 17 16 15 14 13 12 11 10 9 8 7 6 uuuuu. Gu. AAu. GAuuuu. GCAGuu. GAu. AAu. GG**Auuuuuu. Guuu. AGuuuu. Gu. Auuuu. GAAGuu. Au. Auu. Gu -----G-AA-A-GA----GCAG--GA-AA-GGUUA------G--G---G---AG----G-A----GAAG--A--A-A--G--G 70 + -- - ----- +- -- -- - - + -- ---+- - - 106 5 4 3 2 1 GAAAuu. G**Guuu. UGuu. A**UUGGAGUUAUAGAAUAAGAUCAAAUAAGAAAA GAAA--GUUG---UG--AUUUUGGAGUUAUAGAAUAAGAUCAAAUAAGAAAA - ---- - +--- --+- ------- 138 107 ---+ - - Fig. S 8

ES + 90 + + 110 + + 130 + Fig. S 9 3 - 764 - + 108 - + 1311 - 1615 - 18 - 323028272624222019 - + + T-str 51 (ES 54) 3 - + + 764 - + 70 + 108 - + + 1311 - + 50 + 1615 - T-str 31 + + 18 - 0 * 323028272624222019 - 600 + 393735 33 - +. 393735 33 - -Tet +Tet day 3 +Tet day 4 4846 444341 0 RPS 12 4846 444341 *** T-str 51 (ES 54) 50 49 - KH 2 F 1 -RNAi 50 49 - 20 - 40 5251 - SITE-BY-SITE EDITS (%) 60 - B 80 5251 - ES 72 706866 646260585654 53 - 31 72 706866 646260585654 53 - CUM. EDITS A 100 TOTAL EDITS mt. RNA ** * *** + 151 3000 500 2500 400 2000 300 1500 200 100 500 + 151 0

ES T-str 31 + + 50 + + 70 + + 90 + 110 + 3 - 764 - + 3 - + 764 - + 130 108 - + 108 - 1311 - 1615 - 18 - + 1311 - 1615 - + + 18 - + 222019 - + 323028272624 - + 393735 33 - + 4846 444341 + 323028272624 - B 700 T-str 51 (ES 54) 50 49 - -Tet +Tet day 3 +Tet day 4 393735 33 - ES +. RPS 12 4846 444341 0 KREH 2 -RNAi 50 49 - 0 - 20 *** - 40 5251 - 31 72 706866 646260585654 53 - SITE-BY-SITE EDITS (%) 80 5251 - 72 706866 646260585654 53 - CUM. EDITS A 100 TOTAL EDITS mt. RNA 60 * + 151 T-str 51 (ES 54) 3000 600 2500 400 2000 300 1500 200 100 500 + 151 0 Fig. S 10

A 3. 0 T-str 48 (ES 57) RPS 12 2. 5 T-str 80 (ES 46) INC/COR 2. 0 INC/COR KH 2 F 1 -RNAi mt. RNA -Tet +Tet day 3 +Tet day 4 1. 5 1. 0 0. 5 31 0 CUM. INC/COR B C 16 14 151 * ** ** 14 8 12 10 8 6 4 2 2 0 0 12 10 12 * ** 10 CUM. INC/COR 16 KH 2 F 1 -RNAi 12 ** KREH 2 -RNAi 10 8 8 6 6 4 4 2 2 0 T-str 31 0 50 70 90 110 130 151 Fig. S 11

ES 1 + 70 + + ** + 90 + 531 - 2 531 - + 1086 - INC/COR mt. RNA A 6 1086 - + 22201816151312 - 4 2523 -24 - 2726 - INC/COR 5 25242322201816151312 - + T-str 59 0 2726 - 25 3129 - 3433 - + 3129 - B 0 3433 - ES 36 - 59 36 - CUM. INC/COR A KH 2 F 1 -RNAi -Tet +Tet day 3 +Tet day 4 3 102 106 103 107 108 109 + + 110 115 * 20 15 10 5 115 Fig. S 12