N-terminal Ago-binding domain of GW182 contains a tryptophan-rich region that confer binding to the CCR4-NOT complex.
Genes Cells
; 27(9): 579-585, 2022 Sep.
Article
in En
| MEDLINE
| ID: mdl-35822830
ABSTRACT
GW182 family proteins are a key component of microRNA-protein complex eliciting translational repression and/or degradation of microRNA-targets. The microRNAs in complex with Argonaute proteins bind to target mRNAs, and GW182 proteins are recruited by association with Argonaute proteins. The GW182 protein acts as a scaffold that links the Argonaute protein to silencing machineries including the CCR4-NOT complex which accelerates deadenylation and inhibits translation. The carboxyl-terminal effector domain of GW182 protein, also called the silencing domain, has been shown to bind to the subunits of the CCR4-NOT complex, the CNOT1 and the CNOT9. Here we show that a small region within the amino-terminal Argonaute-binding domain of human GW182/TNRC6A can associate with the CCR4-NOT complex. This region resides between the two Argonaute-binding sites and contains reiterated GW/WG-motifs. Alanine mutation experiments showed that multiple tryptophan residues are required for the association with the CCR4-NOT complex. Furthermore, co-expression and immunoprecipitation assays suggested that the CNOT9 subunit of the CCR4-NOT complex is a possible binding partner of this region. Our work, taken together with previous studies, indicates that the human GW182 protein contains multiple binding interfaces to the CCR4-NOT complex.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Autoantigens
/
RNA-Binding Proteins
/
MicroRNAs
/
Argonaute Proteins
Limits:
Humans
Language:
En
Journal:
Genes Cells
Journal subject:
BIOLOGIA MOLECULAR
Year:
2022
Type:
Article
Affiliation country:
Japan