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Status
Public on Sep 07, 2006
Title
Position-specific chemical modification of siRNAs reduces "off-target" transcript silencing
Organism
Homo sapiens Experiment type
Expression profiling by array
Summary
Transfected siRNAs regulate numerous transcripts sharing limited complementarity to the RNA duplex. This unintended (“off-target”) silencing can hinder the use of RNAi to define gene function. Here we describe position-specific, sequence-independent chemical modifications that reduced silencing of partially-complementary transcripts by all siRNAs tested. Silencing of perfectly-matched targets was unaffected by these modifications. The chemical modification also reduced off-target phenotypes in growth inhibition studies. Key to the modification was 2’-O-methyl ribosyl substitution at position 2 in the guide strand, which reduced silencing of most off-target transcripts with complementarity to the seed region of the siRNA guide strand. The sharp position-dependence of 2’-O-methyl ribosyl modification contrasts with the broader position dependence of base pair substitutions within the seed region, suggesting a role for position 2 of the guide strand distinct from its effects on pairing to target transcripts.
Overall design
Please see RNA. 2006 Jul;12(7):1197-205 for details. We used consensus genelists for clustering; please see attached tables for genelists.
Contributor(s)
Jackson AL , Burchard J , Leake D , Reynolds A , Schelter J , Guo J , Johnson JM , Lim L , Karpilow J , Nichols K , Marshall W , Khvorova A , Linsley PS Citation(s)
16682562 Submission date
Sep 05, 2006
Last update date
Nov 05, 2014
Contact name
Aimee Jackson
Organization name
Regulus Therapeutics
Street address
1896 Rutherford Rd
City
Carlsbad
State/province
CA
ZIP/Postal code
92008
Country
USA
Platforms (2)
Samples (61)
GSM134317 HeLa mock-a vs. HeLa PIK3CA-2629-a
GSM134318 HeLa mock-a vs. HeLa PIK3CA-2629-AS_pos2_modified-a
GSM134319 HeLa mock-a vs. HeLa MPHOSPH1-2692-a
GSM134320 HeLa mock-a vs. HeLa MPHOSPH1-2692-AS_pos2_modified-a
GSM134321 HeLa mock-a vs. HeLa SOS1-1582-a
GSM134322 HeLa mock-a vs. HeLa SOS1-1582-AS_pos2_modified-a
GSM134323 HeLa mock-a vs. HeLa PRKCE-1295-a
GSM134324 HeLa mock-a vs. HeLa PRKCE-1295-AS_pos2_modified-a
GSM134325 HeLa mock-a vs. HeLa VHL-2651-a
GSM134326 HeLa mock-a vs. HeLa VHL-2651-AS_pos2_modified-a
GSM134327 HeLa mock-a vs. HeLa VHL-2652-a
GSM134328 HeLa mock-a vs. HeLa VHL-2652-AS_pos2_modified-a
GSM134329 HeLa mock-b vs. HeLa PIK3CA-2629-AS_pos2_modified-b
GSM134330 HeLa mock-b vs. HeLa MPHOSPH1-2692-b
GSM134331 HeLa mock-b vs. HeLa MPHOSPH1-2692-AS_pos2_modified-b
GSM134332 HeLa mock-b vs. HeLa SOS1-1582-b
GSM134333 HeLa mock-b vs. HeLa SOS1-1582-AS_pos2_modified-b
GSM134334 HeLa mock-b vs. HeLa PRKCE-1295-b
GSM134335 HeLa mock-b vs. HeLa PRKCE-1295-AS_pos2_modified-b
GSM134336 HeLa mock-b vs. HeLa VHL-2651-b
GSM134337 HeLa mock-b vs. HeLa VHL-2651-AS_pos2_modified-b
GSM134338 HeLa mock-b vs. HeLa VHL-2652-b
GSM134339 HeLa mock-b vs. HeLa VHL-2652-AS_pos2_modified-b
GSM134521 Hela, mock, 24 hr vs. HeLa, 193-MAPK14, 24 hr, unmodified
GSM134522 HeLa, mock, 18 hr vs. HeLa, MAPK14-193, unmodified, 100nM, 18 hr
GSM134523 HeLa, mock, 18 hr vs. HeLa, MPHOSPH1-202, unmodified, 100nM, 18 hr
GSM134524 HeLa, mock, 18 hr vs. HeLa, MPHOSPH1-202, unmodified, 10nM, 18 hr
GSM134525 HeLa, mock, 18 hr vs. HeLa, MPHOSPH1-202, AS_pos1+2_modified, 100nM, 18 hr
GSM134526 HeLa, mock, 18 hr vs. HeLa, MPHOSPH1-202, AS_pos1+2_modified, 10nM, 18 hr
GSM134527 Hela, mock, 18hr vs. Hela, MAPK14-193, AS_pos1+2_modified, 18hr
GSM134528 Hela, mock, 18hr vs. Hela, MAPK14-193, AS_pos2+3_modified, 18hr
GSM134529 Hela, mock, 18hr vs. Hela, MAPK14-193, AS_pos3+4_modified, 18hr
GSM134530 Hela, mock, 18hr vs. Hela, MAPK14-193, AS_pos4+5_modified, 18hr
GSM134531 Hela, mock, 18hr vs. Hela, MAPK14-193, AS_pos5+6_modified, 18hr
GSM134532 Hela, mock, 18hr vs. Hela, MAPK14-193, AS_pos6+7_modified, 18hr
GSM134533 Hela, mock, 18hr vs. Hela, MAPK14-193, AS_pos7+8_modified, 18hr
GSM134534 Hela, mock, 18hr vs. Hela, MAPK14-193, AS_pos8+9_modified, 18hr
GSM134535 Hela, mock, 18hr vs. Hela, MAPK14-193, AS_pos9+10_modified, 18hr
GSM134536 Hela, mock, 18hr vs. Hela, MAPK14-193, AS_pos10+11_modified, 18hr
GSM134537 Hela, mock, 18hr vs. Hela, MAPK14-193, AS_pos1_modified, 18hr
GSM134538 Hela, mock, 18hr vs. Hela, MAPK14-193, AS_pos2_modified, 18hr
GSM134539 Hela, mock, 18hr vs. Hela, MAPK14-193, AS_pos11+12_modified, 18hr
GSM134540 HeLa, mock, 20 hr vs. HeLa, 193-MAPK14, unmodified, 20 hr
GSM134541 HeLa, mock, 20 hr vs. HeLa, 193-MAPK14, AS_pos1+2_modified, 20 hr
GSM134542 Hela, mock, 18hr vs. Hela, MAPK14-193, AS_pos8+9_modified-b, 18hr
GSM134543 Hela, mock, 18hr vs. Hela, MAPK14-193, AS_pos1_modified-b, 18hr
GSM134544 HeLa, mock, 24hr vs. HeLa, MAPK14-193, AS_pos1+2_modified, 24hr
GSM134545 HeLa, mock, 24hr vs. HeLa, MAPK14-193, unmodified, 24hr
GSM134546 HeLa, mock, 20hr vs. HeLa, MAPK14-193, unmodified, 20hr
GSM134547 HeLa, mock, 24hr vs. HeLa, MAPK14-193, unmodified, 100nM, 24 hr
GSM134548 HeLa, mock, 24hr vs. HeLa, MAPK14-193, unmodified, 10nM, 24 hr
GSM134549 HeLa, mock, 24hr vs. HeLa, MAPK14-193, AS_pos1+2_modified, 100nM, 24 hr
GSM134550 HeLa, mock, 24hr vs. HeLa, MAPK14-193, AS_pos1+2_modified, 10nM, 24 hr
GSM134551 HeLa, mock, 24hr vs. HeLa, MPHOSPH1-202, unmodified, 100nM, 24 hr
GSM134552 HeLa, mock, 24hr vs. HeLa, MPHOSPH1-202, unmodified, 10nM, 24 hr
GSM134553 HeLa, mock, 24hr vs. HeLa, MPHOSPH1-202, AS_pos1+2_modified, 100nM, 24 hr
GSM134554 HeLa, mock, 24hr vs. HeLa, MPHOSPH1-202, AS_pos1+2_modified, 10nM, 24 hr
GSM430347 HeLa, mock, 24hr vs. HeLa, MAPK14-193, normal, 1nM, 24 hr
GSM430348 HeLa, mock, 24hr vs. HeLa, MAPK14-193, normal, 0.1nM, 24 hr
GSM430349 HeLa, mock, 24hr vs. HeLa, MPHOSH1-202, normal, 1nM, 24 hr
GSM430350 HeLa, mock, 24hr vs. HeLa, MPHOSH1-202, normal, 0.1nM, 24 hr
Relations BioProject
PRJNA97111
mphosph1_responders_non-responders_genelist header descriptions Primary Sequence Name Sequence Code
Data table Primary Sequence Name Sequence Code FGF2
NM_002006
KIAA1411
AB037832
Contig27741_RC
HPRT1
NM_000194
ARF4
NM_001660
MAP1LC3B
Contig4781_RC
MCL1
L08246
ARL5B
AL133611
RAB18
AK001555
SDHB
NM_003000
MARCKS
Contig57231_RC
DPY19L4
AL049962
Contig50584_RC
YWHAQ
NM_006826
PJA2
NM_014819
SLC31A1
Contig20901_RC
MTX3
Contig53962_RC
ECT2
NM_018098
SIX4
Contig48935_RC
C7orf36
Contig51078_RC
405 7 Kbytes .mapk14_responders_nonresponders_genelist header descriptions Primary Sequence Name Sequence Code
Data table Primary Sequence Name Sequence Code LOC441347
AL050136
ARMC8
NM_015396
RBM7
NM_016090
NPTN
NM_017455
SETD7
Contig57582_RC
NPTN
NM_012428
CRIPT
NM_014171
UBP1
NM_014517
ANKFY1
AB033081
RTN4R
Contig45454_RC
LOC440203
Contig54980_RC
CDC42SE2
AF131831
N-PAC
NM_018459
C14orf46
Contig41736_RC
BTRC
Contig65663
ZNF706
Contig46375_RC
ARPC5L
Contig3398_RC
TEAD1
AL133574
NPR3
NM_000908
GPR30
NM_001505
52 <1 Kbytes .mod_various_siRNAs_genelist header descriptions Accession number
Data table Accession number HSS00311627
NM_012090
NM_033044
NM_031463
HSS00248137
NM_015344
AK025810
BC015594
NM_017588
NM_052821
HSS00079227
NM_018319
AK001820
HSS00169052
NM_018718
NM_025234
NM_013437
NM_024937
NM_052965
NM_032351
3201 36 Kbytes .Chem_mod_walk_genelist header descriptions Primary Sequence Name Sequence Code
Data table Primary Sequence Name Sequence Code LOC441347
AL050136
ARMC8
NM_015396
RBM7
NM_016090
NPTN
NM_017455
SETD7
Contig57582_RC
NPTN
NM_012428
CRIPT
NM_014171
EXPH5
AB014524
UBP1
NM_014517
ANKFY1
AB033081
RTN4R
Contig45454_RC
LOC440203
Contig54980_RC
CDC42SE2
AF131831
KLHL24
Contig50396_RC
N-PAC
NM_018459
C20orf11
Contig1924_RC
C14orf46
Contig41736_RC
BTRC
Contig65663
ZNF706
Contig46375_RC
ARPC5L
Contig3398_RC
52 <1 Kbytes .Supplementary file Size Download File type/resource GSE5769_RAW.tar
180.0 Kb
(http) (custom) TAR
Processed data included within Sample table
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