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Updated: May 26, 2026
10:37
Toeprinting Analysis of Translation Initiation Complex Formation on Mammalian mRNAs
Published on: May 10, 2018
Stringency of start codon selection modulates autoregulation of translation initiation factor eIF5
Gary Loughran1, Matthew S Sachs, John F Atkins
1BioSciences Institute, University College Cork, Ireland.
Nucleic Acids Research
|December 14, 2011
Summary
High levels of translation initiation factor eIF5 decrease start codon selection stringency, while eIF1 increases it. eIF5 autoregulates its own synthesis by translating upstream open reading frames, forming a feedback loop with eIF1 to stabilize translation initiation.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Translation initiation is a critical regulatory step in gene expression.
- Start codon selection is governed by interactions between translation initiation factors like eIF1 and eIF5.
- The stringency of start codon selection ensures accurate protein synthesis.
Purpose of the Study:
- To investigate the role of eukaryotic initiation factor 5 (eIF5) levels in regulating translation initiation.
- To elucidate the mechanism of eIF5 autoregulation.
- To understand the interplay between eIF1 and eIF5 in controlling start codon selection.
Main Methods:
- Experiments in human cells to manipulate intracellular levels of eIF1 and eIF5.
- Analysis of translation of upstream open reading frames (uORFs) in eIF5 mRNA.
- Assessment of start codon selection stringency under varying factor concentrations.
Main Results:
- Elevated eIF5 levels reduced start codon selection stringency.
- Elevated eIF1 levels increased start codon selection stringency.
- High eIF5 induced translation of inhibitory uORFs in its own mRNA, leading to reduced eIF5 synthesis.
- eIF5 autoregulation mechanism is evolutionarily conserved.
Conclusions:
- eIF5 autoregulates its synthesis through translation of uORFs in poor sequence contexts.
- Auto- and cross-regulation between eIF1 and eIF5 form a feedback loop.
- This regulatory loop stabilizes the stringency of start codon selection in eukaryotic cells.
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