| First Author | Vickers TA | Year | 2009 |
| Journal | Nucleic Acids Res | Volume | 37 |
| Issue | 20 | Pages | 6927-41 |
| PubMed ID | 19767612 | Mgi Jnum | J:173016 |
| Mgi Id | MGI:5009477 | Doi | 10.1093/nar/gkp735 |
| Citation | Vickers TA, et al. (2009) Off-target and a portion of target-specific siRNA mediated mRNA degradation is Ago2 'Slicer' independent and can be mediated by Ago1. Nucleic Acids Res 37(20):6927-41 |
| abstractText | It is known that siRNAs are capable of reducing expression of non-target genes due to the interaction of the siRNA guide strand with a partially complementary site on the 'off-target' mRNA. In the current study, we show that reduction of cellular Ago2 levels has no effect on off-target reduction of endogenous genes and that off-target degradation of mRNA can occur even in an Ago2 knockout cell line. Using antisense mediated reduction of Ago proteins and chemically modified cleavage- and binding-deficient siRNAs, we demonstrate that siRNA mediated off-target reduction is Ago2 cleavage independent, but does require siRNA interaction with either Ago1 or Ago2 and the RISC-loading complex. We also show that depletion of P-body associated proteins results in a reduction of off-target siRNA-mediated degradation of mRNA. Finally, we present data suggesting that a significant portion of on-target siRNA activity is also Ago2 cleavage independent, however, this activity does not appear to be P-body associated. |
