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Updated: Sep 28, 2025
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Study of Protein-protein Interactions in Autophagy Research
Published on: September 9, 2017
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Upstream open reading frames mediate autophagy-related protein translation
Ying Yang1, Damián Gatica1, Xu Liu1
1Department of Molecular, Cellular and Developmental Biology, and Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Autophagy
|April 1, 2022
Summary
Autophagy regulation is controlled by upstream open reading frames (uORFs) in yeast and human cells. These uORFs suppress translation under nutrient-rich conditions and activate it during starvation, maintaining cellular homeostasis.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Macroautophagy/autophagy is a vital cellular process for maintaining homeostasis, regulated by autophagy-related (Atg) proteins.
- While transcriptional regulation of autophagy is well-studied, translational control mechanisms remain largely unexplored.
Purpose of the Study:
- To investigate the role of upstream open reading frames (uORFs) in the translational control of autophagy-related (Atg) genes.
- To determine if uORF-mediated translational regulation is conserved across species, from yeast to humans.
Main Methods:
- Analysis of canonical and non-canonical uORFs in the 5' untranslated regions (UTRs) of yeast and human ATG genes.
- Experimental validation of uORF function in controlling downstream coding sequence (CDS) translation under different nutrient conditions.
Main Results:
- Canonical uORFs suppress the translation of essential yeast Atg proteins, including Atg13, under nutrient-rich conditions.
- uORF-mediated translational control is activated during nitrogen-starvation conditions in yeast.
- Predicted human ATG4B and ATG12 non-canonical uORFs were found to suppress downstream CDS translation.
Conclusions:
- uORF-mediated translational control is a conserved mechanism regulating multiple ATG genes from yeast to humans.
- This regulatory mechanism allows some ATG genes to bypass general translational suppression during stress, ensuring proper autophagy levels.
- uORFs represent a significant layer of post-transcriptional regulation in the autophagy pathway.
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