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Updated: May 8, 2026
08:23
De novo Identification of Actively Translated Open Reading Frames with Ribosome Profiling Data
Published on: February 18, 2022
Gene expression regulation by upstream open reading frames and human disease
Cristina Barbosa1, Isabel Peixeiro, Luísa Romão
1Departamento de Genética Humana, Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisboa, Portugal.
Plos Genetics
|August 17, 2013
Summary
Upstream open reading frames (uORFs) regulate gene expression and translation. Dysregulation of uORFs is linked to various human diseases, highlighting their importance in health and illness.
Area of Science:
- Molecular Biology
- Genetics
- Gene Regulation
Background:
- Upstream open reading frames (uORFs) are regulatory elements found in eukaryotic messenger RNAs (mRNAs).
- uORFs can influence the expression of downstream main open reading frames (ORFs) by affecting mRNA stability and translation.
- Approximately half of human transcripts contain uORFs, underscoring their prevalence.
Purpose of the Study:
- To review the mechanisms by which uORFs regulate gene expression.
- To explore the impact of uORFs on cellular responses to stress.
- To emphasize the role of disturbed uORF-mediated translational control in human diseases, focusing on genotype-phenotype correlations.
Main Methods:
- Literature review of genetic and bioinformatic studies.
- Analysis of mechanisms of uORF-mediated gene regulation.
- Case illustrations of genotype-phenotype correlations in uORF-related disorders.
Main Results:
- uORFs significantly impact gene expression through mRNA decay and translational regulation.
- Disturbed uORF control is implicated in the etiology of malignancies, metabolic disorders, neurologic conditions, and inherited syndromes.
- Specific examples demonstrate the link between uORF mutations and disease phenotypes.
Conclusions:
- uORFs are critical regulators of gene expression with profound implications for human health.
- Understanding uORF function and mutations is crucial for advancing the diagnosis, prognosis, and treatment of numerous disorders.
- Further research into uORF-altering mutations will solidify genotype-phenotype associations and improve clinical outcomes.
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