Expression profiling reveals off-target gene regulation by RNAi.
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.
Jackson
Aimee L
AL
Rosetta Inpharmatics LLC, 12040 115th Avenue NE, Kirkland, Washington 98034, USA. aimee_jackson@merck.com
Bartz
Steven R
SR
Schelter
Janell
J
Kobayashi
Sumire V
SV
Burchard
Julja
J
Mao
Mao
M
Li
Bin
B
Cavet
Guy
G
Linsley
Peter S
PS
D001483:Base Sequence; D017124:Conserved Sequence; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D020868:Gene Silencing; D018390:Gene Targeting / Q000379:methods*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D034622:RNA Interference; D012333:RNA, Messenger; D034741:RNA, Small Interfering / Q000235:genetics*; D014170:Transformation, Genetic
D012333:RNA, Messenger; D034741:RNA, Small Interfering