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mi RISC and the CCR 4– NOT complex silence mRNA targets independently of 43S ribosomal scanning
Author(s) -
KuzuoğluÖztürk Duygu,
Bhandari Dipankar,
Huntzinger Eric,
Fauser Maria,
Helms Sigrun,
Izaurralde Elisa
Publication year - 2016
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201592901
Subject(s) - biology
mi RNA s 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 AGO s mediate these effects through the sequential recruitment of GW 182 proteins, the CCR 4– NOT deadenylase complex and the translational repressor and decapping activator DDX 6. An alternative model posits that AGO s repress translation by interfering with eIF 4A function during 43S ribosomal scanning and that this mechanism is independent of GW 182 and the CCR 4– NOT complex in Drosophila melanogaster . Here, we show that mi RNA s, AGO s, GW 182, the CCR 4– NOT complex, and DDX 6/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 RNA s to mediate silencing. This mechanism does not require eIF 4A function during ribosomal scanning.