Off-target and a portion of target-specific siRNA mediated mRNA degradation is Ago2 ‘Slicer’ independent and can be mediated by Ago1
| العنوان: | Off-target and a portion of target-specific siRNA mediated mRNA degradation is Ago2 ‘Slicer’ independent and can be mediated by Ago1 |
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| المؤلفون: | Stanley T. Crooke, Josh G. Nichols, Walt F. Lima, Timothy A. Vickers, Hongjiang Wu, Peter S. Linsley |
| المصدر: | Nucleic Acids Research |
| بيانات النشر: | Oxford University Press (OUP), 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Ribonuclease III, Small interfering RNA, Class I Phosphatidylinositol 3-Kinases, RNA Stability, Eukaryotic Initiation Factor-2, Biology, Cleavage (embryo), Mice, Phosphatidylinositol 3-Kinases, RNA interference, Genetics, Animals, Humans, RNA, Messenger, Eukaryotic Initiation Factors, RNA, Small Interfering, Cells, Cultured, Mice, Knockout, Messenger RNA, Gene Expression Profiling, RNA, Argonaute, Molecular biology, Cell biology, Cell culture, Argonaute Proteins, RNA Interference, Cytokinesis |
| الوصف: | 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. |
| تدمد: | 1362-4962 0305-1048 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::babb354d1e198913fc90dccc601fe5e2 https://doi.org/10.1093/nar/gkp735 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....babb354d1e198913fc90dccc601fe5e2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13624962 03051048 |
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