mi RISC and the CCR 4– NOT complex silence mRNA targets independently of 43S ribosomal scanning

miRNAs 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...

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Bibliographic Details
Published in:The EMBO journal 2016-06, Vol.35 (11), p.1186-1203
Main Authors: Kuzuoğlu‐Öztürk, Duygu, Bhandari, Dipankar, Huntzinger, Eric, Fauser, Maria, Helms, Sigrun, Izaurralde, Elisa
Format: Article
Language:English
Subjects:
Argonaute Proteins
Autoantigens
Cell Line
DEAD-box RNA Helicases
Drosophila Proteins
Humans
Life Sciences
MicroRNAs
Proto-Oncogene Proteins
Ribosomes
RNA, Messenger
RNA-Binding Proteins
Transcription Factors
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Summary:miRNAs 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 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 indicate a common mechanism used by these proteins and miRNAs to mediate silencing. This mechanism does not require eIF4A function during ribosomal scanning.
ISSN:0261-4189
1460-2075
DOI:10.15252/embj.201592901