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Updated: Jun 25, 2025
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Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
Published on: May 1, 2020
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eIF4A1 enhances LARP1-mediated translational repression during mTORC1 inhibition.
Yuichi Shichino1, Tomokazu Yamaguchi2,3, Kazuhiro Kashiwagi4
1RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Wako, Japan. yuichi.shichino@riken.jp.
Nature Structural & Molecular Biology
|May 21, 2024
Summary
Eukaryotic translation initiation factor 4A1 (eIF4A1) surprisingly enhances translational repression, particularly for TOP mRNAs, when mTORC1 signaling is inhibited. This finding reveals a novel repressive role for a key translation activator.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Eukaryotic translation initiation factor 4A (eIF4A) is a DEAD-box RNA-binding protein crucial for translation initiation.
- While known for promoting translation, eIF4A's diverse functions, including potential roles in repression, are not fully understood.
Purpose of the Study:
- To investigate the role of eIF4A1 in translational regulation, specifically during mechanistic target of rapamycin complex 1 (mTORC1) inhibition.
- To elucidate the mechanisms by which eIF4A1 modulates protein synthesis under specific cellular conditions.
Main Methods:
- RNA pulldown followed by sequencing to identify eIF4A1-bound mRNAs.
- Ribosome profiling to assess translational efficiency.
- Analysis of interactions between eIF4A1, LARP1, and TOP mRNAs.
Main Results:
- eIF4A1 preferentially binds to mRNAs with terminal oligopyrimidine (TOP) motifs, which are translationally repressed upon mTORC1 inhibition.
- Deletion of EIF4A1 weakened the repression of TOP mRNA translation following mTORC1 inactivation.
- eIF4A1 enhances the interaction between TOP mRNAs and LARP1, leading to increased translational repression.
Conclusions:
- eIF4A1 plays a significant role in translational repression, particularly for TOP mRNAs, in response to mTORC1 inhibition.
- This study highlights the multimodal functions of eIF4A1, demonstrating its capacity to act as a repressor through interaction with inhibitory partners like LARP1.
- Provides a novel example of a general translation activator having a repressive function in specific contexts.
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