Title: The CCR4-NOT complex is a major downstream effector complex of miRNA-mediated gene silencing
Speaker: Duygu Kuzuoğlu-Öztürk
Date/Time: November 18, Wednesday, 12:40 - 13:30
Place: FENS L035
Abstract: miRNAs associate with Argonaute (AGO) proteins to silence the expression of mRNA targets by inhibiting translation and eliciting deadenylation, decapping and mRNA degradation. A current model for silencing indicates that AGOs mediate these effects through the sequential recruitment of GW182 proteins, the CCR4-NOT deadenylase complex and the translational repressor and decapping activator DDX6. An alternative model posits that AGOs repress translation by interfering with eIF4A function during 43S ribosomal scanning and that this mechanism is independent of GW182 and the CCR4-NOT complex in Drosophila melanogaster. Here we show that miRNAs, AGOs, GW182, the CCR4-NOT complex and DDX6/Me31B repress and degrade polyadenylated mRNA targets that are translated via scanning independent mechanisms in both human and Dm cells. This and additional observations point to a common mechanism used by these proteins and miRNAs to mediate silencing. This mechanism does not require eIF4A function during ribosomal scanning.