title: Expression profiling reveals off-target gene regulation by RNAi.
abstract: 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.
authors.affiliation: Rosetta Inpharmatics LLC, 12040 115th Avenue NE, Kirkland, Washington 98034, USA. aimee_jackson@merck.com
authors.forename: Aimee L
authors.initials: AL
authors.lastname: Jackson
authors.forename: Steven R
authors.initials: SR
authors.lastname: Bartz
authors.forename: Janell
authors.initials: J
authors.lastname: Schelter
authors.forename: Sumire V
authors.initials: SV
authors.lastname: Kobayashi
authors.forename: Julja
authors.initials: J
authors.lastname: Burchard
authors.forename: Mao
authors.initials: M
authors.lastname: Mao
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Guy
authors.initials: G
authors.lastname: Cavet
authors.forename: Peter S
authors.initials: PS
authors.lastname: Linsley
mesh_terms: 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
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering