Chemical Modification of siRNA Bases to Probe and Enhance RNA Interference
TLDR
Less common chemical modifications of the RNA nucleobases have the potential to lend insight into the mechanism of gene silencing and to lead to novel methods to overcome off-target effects that arise due to deleterious protein binding or mis-targeting of mRNA.Abstract:
Considerable attention has focused on the use of alternatives to the native ribose and phosphate backbone of small interfering RNAs for therapeutic applications of the RNA interference pathway. In this synopsis, we highlight the less common chemical modifications, namely, those of the RNA nucleobases. Base modifications have the potential to lend insight into the mechanism of gene silencing and to lead to novel methods to overcome off-target effects that arise due to deleterious protein binding or mis-targeting of mRNA.read more
Citations
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TL;DR: In this paper, it was shown that miRNAs are incorporated indiscriminately of their sequence into Ago1 through Ago4 containing microRNPs (miRNPs) and endonuclease activity is exclusively associated with Ago2.
Journal Article
Human argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs
Gunter Meister,Markus Landthaler,Agnieszka Patkaniowska,Yair Dorsett,Grace Teng,Thomas Tuschl +5 more
TL;DR: The authors' results suggest that miRNAs are incorporated indiscriminately of their sequence into Ago1 through Ago4 containing microRNPs (miRNPs), and the specific role of Ago2 in guiding target RNA cleavage was confirmed by siRNA-based depletion of individual Ago members in combination with a sensitive positive-readout reporter assay.
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