3′ UTR seed matches, but not overall identity, are associated with RNAi off-targets

By Amanda Birmingham, E. Anderson, A. Reynolds, Diane Ilsley-Tyree, D. Leake, Yuriy Fedorov, S. Baskerville, E. Maksimova, K. Robinson, J. Karpilow and 2 more. Nature Methods, 2006

917 citations recorded by the source corpus.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/8a00208a138a4775355030b36b604a2f41e23bd8

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Citations in the corpus

Gene silencing in plants using artificial microRNAs and other small RNAs. (2008, background): “When this phenomenon was investigated in more detail, again in mammalian cells, a strong correlation between unintended targets, generally called ‘off-targets’, and short stretches of complementarity to the siRNA in the 3¢ UTRs of the affected transcripts was found (Birmingham et al., 2006).”
RNAi therapeutics: a potential new class of pharmaceutical drugs (2006, background): “Although the seed region seems to be critical for mRNA recognition, notable mRNA cleavage requires more extensive base pairing between the siRNA and the target 32 .”
Recognizing and avoiding siRNA off-target effects for target identification and therapeutic application (2010, background): “Subsequent studies exploring siRNAs targeting a diverse set of transcripts showed that each siRNA downregulated a set of transcripts that was enriched for transcripts with 3′ UTR complementarity to the 5′ portion of the corresponding siRNA guide stran”
RNAi-Based Insecticidal Crops: Potential Effects on Nontarget Species (2013, background): “…use of the intrinsic rate of population growth, which can be measured in the laboratory and which integrates survival, development time, reproduction, and sex ratio to generate a clearer picture of how a plant- incorporated toxin affects a nontarget species (Bøhn et al. 2010, Li and Romeis 2010).”
Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2. (2007, background): “However, many conclusions regarding base-pairing have been drawn from overexpression of miRNAs, in which nonphysiologic miRNA:mRNA interactions may occur and siRNA-like off-target effects may be observed (Birmingham et al., 2006; Jackson et al., 2006).”
Analysis of cell-based RNAi screens (2006, background): “Sequence similarity as small as heptamers with perfect matches in the 3'-untranslated region can mediate translational inhibition of mRNAs through a miRNA pathway [37].”
The promises and pitfalls of RNA-interference-based therapeutics (2009, neutral): “; as few as six or seven nucleotides complementary to the seed region could result in a specific off-target effec”
RNAi therapeutics: principles, prospects and challenges. (2007, background): “However, in term of predicting offtargets the picture is far from complete as a large number of genes with good seed match remain unaffected [62].”
Predicting effective microRNA target sites in mammalian mRNAs (2015, neutral): “…16012097016668, 16012097016669, 16012097017938, 16012097017939, 16012097017952, 16012097017953, 16012097018568, 251209725411) (Lim et al., 2005; Birmingham et al., 2006; Schwarz et al., 2006; Jackson et al., 2006a; Jackson et al., 2006b; Grimson et al., 2007; Anderson et al., 2008) Figure…”