PathwayStep346 PathwayStep344 PathwayStep345 Binding of Exactly Matching Target RNAs by Nonendonucleolytic RISC Cleavage of Target RNAs by Endonucleolytic RISC Binding of Inexactly Matching Target RNAs by RISC. Post-transcriptional Silencing By Small RNAs Authored: May, B, 2009-06-10 Edited: May, B, 2009-06-10 Pubmed12154197 Pubmed15260970 Pubmed15284456 Pubmed16510870 Pubmed17128271 Pubmed17197185 Pubmed17560368 Pubmed17632058 Pubmed18692607 Pubmed19174539 Pubmed19239886 Pubmed19330724 Pubmed19412884 Pubmed19477631 Reactome Database ID Release 43426496 Reactome, http://www.reactome.org ReactomeREACT_118699 Reviewed: Tomari, Y, 2012-02-10 Small RNAs act with components of the RNA-induced silencing complex (RISC) to repress expression of mRNAs (reviewed in Nowotny and Yang 2009, Chua et al. 2009). Two mechanisms exist: 1) cleavage of target RNAs by complexes containing Argonaute2 (AGO2) and a guide RNA that exactly matches the target mRNA and 2) inhibition of translation of target RNAs by complexes containing AGO2 and an inexactly matching guide RNA or by complexes containing a nonendonucleolytic Argonaute (AGO1, AGO3, or AGO4) and a guide RNA of exact or inexact match. Small interfering RNAs (siRNAs) and microRNAs (miRNAs) can serve as guide RNAs in both types of mechanism. <br>RNAi also appears to direct chromatin modifications that cause transcriptional gene silencing (reviewed in Verdel et al. 2009).