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Updated: Dec 10, 2025

De novo Identification of Actively Translated Open Reading Frames with Ribosome Profiling Data
Published on: February 18, 2022
Conserved Upstream Open Reading Frame Nascent Peptides That Control Translation
Thomas E Dever1, Ivaylo P Ivanov1, Matthew S Sachs2
1Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA; email: thomas.dever@nih.gov, ivaylo.ivanov@nih.gov.
Upstream open reading frames (uORFs) encode peptides that regulate gene expression. These peptides stall ribosomes in response to metabolites, controlling messenger RNA translation and levels across diverse species.
Area of Science:
- Molecular Biology
- Gene Regulation
- Biochemistry
Background:
- Cells adjust gene expression via transcriptional and posttranscriptional mechanisms.
- Messenger RNA (mRNA) translation offers rapid, gene-specific control in response to environmental changes.
- Upstream open reading frames (uORFs) are established regulators of mRNA translation.
Purpose of the Study:
- To review the functions of evolutionarily conserved uORF-encoded peptides.
- To highlight how uORF peptides modulate mRNA translation and levels.
- To examine the role of uORF peptides in metabolite-responsive gene regulation.
Main Methods:
- Literature review of recent studies on uORF-encoded peptides.
- Analysis of conserved uORF functions across bacteria, fungi, mammals, and plants.
- Examination of ribosome stalling as a regulatory mechanism.
Main Results:
- Conserved uORF-encoded peptides respond to specific metabolites.
- These peptides induce ribosome stalling to regulate mRNA translation.
- Ribosome stalling mediated by uORF peptides can also affect mRNA levels.
- This regulatory mechanism is conserved across diverse eukaryotic and prokaryotic organisms.
Conclusions:
- uORF-encoded peptides are crucial regulators of gene expression.
- Metabolite-sensing uORF peptides provide rapid cellular responses.
- Ribosome stalling is a key mechanism employed by uORF peptides for gene regulation.
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