Cap-binding protein 4EHP effects translation silencing by microRNAs.
Proc Natl Acad Sci U S A
; 114(21): 5425-5430, 2017 05 23.
Article
in En
| MEDLINE
| ID: mdl-28487484
ABSTRACT
MicroRNAs (miRNAs) play critical roles in a broad variety of biological processes by inhibiting translation initiation and by destabilizing target mRNAs. The CCR4-NOT complex effects miRNA-mediated silencing, at least in part through interactions with 4E-T (eIF4E transporter) protein, but the precise mechanism is unknown. Here we show that the cap-binding eIF4E-homologous protein 4EHP is an integral component of the miRNA-mediated silencing machinery. We demonstrate that the cap-binding activity of 4EHP contributes to the translational silencing by miRNAs through the CCR4-NOT complex. Our results show that 4EHP competes with eIF4E for binding to 4E-T, and this interaction increases the affinity of 4EHP for the cap. We propose a model wherein the 4E-T/4EHP interaction engenders a closed-loop mRNA conformation that blocks translational initiation of miRNA targets.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
RNA-Induced Silencing Complex
/
RNA Cap-Binding Proteins
/
MicroRNAs
/
RNA Interference
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2017
Document type:
Article
Affiliation country: