학술논문

mi RISC and the CCR4- NOT complex silence mRNA targets independently of 43S ribosomal scanning.
Document Type
Article
Source
EMBO Journal. 6/1/2016, Vol. 35 Issue 11, p1186-1203. 18p.
Subject
*MESSENGER RNA
*GENE targeting
*RIBOSOMAL RNA
*DROSOPHILA melanogaster
*DEADENYLATION
Language
ISSN
0261-4189
Abstract
mi RNAs associate with Argonaute ( AGO) proteins to silence the expression of mRNA targets by inhibiting translation and promoting deadenylation, decapping, and mRNA degradation. A current model for silencing suggests 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 mi RNAs, 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 indicate a common mechanism used by these proteins and mi RNAs to mediate silencing. This mechanism does not require eIF4A function during ribosomal scanning. [ABSTRACT FROM AUTHOR]