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Updated: Oct 7, 2025
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De novo Identification of Actively Translated Open Reading Frames with Ribosome Profiling Data
Published on: February 18, 2022
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Ribosomal leaky scanning through a translated uORF requires eIF4G2.
Victoria V Smirnova1, Ekaterina D Shestakova2, Daria S Nogina2
1Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119234, Russia.
Nucleic Acids Research
|January 12, 2022
Summary
The translation factor eIF4G2 (DAP5) assists in mRNA scanning beyond the initial cap-binding step, particularly when eIF4G1 dissociates, ensuring translation proceeds efficiently in higher eukaryotes.
Area of Science:
- Molecular Biology
- Gene Expression Regulation
Background:
- eIF4G2 (DAP5/Nat1) is a homolog of eIF4G1, a key translation initiation factor.
- eIF4G2's function is less understood; it doesn't bind eIF4E and is thought to mediate translation during stress.
Purpose of the Study:
- To elucidate the function of eIF4G2 under normal and stress conditions.
- To investigate eIF4G2's role in mRNA scanning and translation initiation.
Main Methods:
- Analysis of translation initiation factors and mRNA scanning dynamics.
- Investigating the interplay between eIF4G1, eIF4G2, and mRNA features like 5' UTRs and upstream ORFs (uORFs).
Main Results:
- eIF4G2 promotes downstream scanning after initial 40S ribosomal subunit recruitment by eIF4G1.
- eIF4G2 facilitates leaky scanning for specific mRNAs, replacing eIF4G1 when it dissociates.
- This mechanism is critical for long 5' UTRs and uORFs common in higher eukaryotes, rescuing stalled scanning complexes.
Conclusions:
- Higher eukaryotes utilize two distinct scanning complexes: a principal one (eIF4G1-mediated) and an accessory one (eIF4G2-mediated) that rescues scanning.
- eIF4G2 plays a crucial role in translation under normal conditions, not just during stress, by ensuring efficient scanning past obstacles.
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