Expression profiling reveals off-target gene regulation by RNAi

被引:1753
作者
Jackson, AL [1 ]
Bartz, SR [1 ]
Schelter, J [1 ]
Kobayashi, SV [1 ]
Burchard, J [1 ]
Mao, M [1 ]
Li, B [1 ]
Cavet, G [1 ]
Linsley, PS [1 ]
机构
[1] Rosetta Inpharmat LLC, Kirkland, WA 98034 USA
关键词
D O I
10.1038/nbt831
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
RNA interference is thought to require near-identity between the small interfering RNA (siRNA) and its cognate mRNA. Here, we used gene expression profiling to characterize the specificity of gene silencing by siRNAs in cultured human cells. Transcript profiles revealed siRNA-specific rather than target-specific signatures, including direct silencing of nontargeted genes containing as few as eleven contiguous nucleotides of identity to the siRNA. These results demonstrate that siRNAs may cross-react with targets of limited sequence similarity.
引用
收藏
页码:635 / 637
页数:3
相关论文
共 7 条
  • [1] Small RNAs make big splash
    Couzin, J
    [J]. SCIENCE, 2002, 298 (5602) : 2296 - 2297
  • [2] Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate
    Elbashir, SM
    Martinez, J
    Patkaniowska, A
    Lendeckel, W
    Tuschl, T
    [J]. EMBO JOURNAL, 2001, 20 (23) : 6877 - 6888
  • [3] Expression profiling using microarrays fabricated by an ink-jet oligonucleotide synthesizer
    Hughes, TR
    Mao, M
    Jones, AR
    Burchard, J
    Marton, MJ
    Shannon, KW
    Lefkowitz, SM
    Ziman, M
    Schelter, JM
    Meyer, MR
    Kobayashi, S
    Davis, C
    Dai, HY
    He, YDD
    Stephaniants, SB
    Cavet, G
    Walker, WL
    West, A
    Coffey, E
    Shoemaker, DD
    Stoughton, R
    Blanchard, AP
    Friend, SH
    Linsley, PS
    [J]. NATURE BIOTECHNOLOGY, 2001, 19 (04) : 342 - 347
  • [4] HUTVAGNER G, 2002, SCIENCE, V237, P2085
  • [5] Micro RNAs are complementary to 3′ UTR sequence motifs that mediate negative post-transcriptional regulation
    Lai, EC
    [J]. NATURE GENETICS, 2002, 30 (04) : 363 - 364
  • [6] Synthetic small inhibiting RNAs:: Efficient tools to inactivate oncogenic mutations and restore p53 pathways
    Martinez, LA
    Naguibneva, I
    Lehrmann, H
    Vervisch, A
    Tchénio, T
    Lozano, G
    Harel-Bellan, A
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (23) : 14849 - 14854
  • [7] Targeted mRNA degradation by double-stranded RNA in vitro
    Tuschl, T
    Zamore, PD
    Lehmann, R
    Bartel, DP
    Sharp, PA
    [J]. GENES & DEVELOPMENT, 1999, 13 (24) : 3191 - 3197