ArticlePLoS genetics2022
Translational buffering by ribosome stalling in upstream open reading frames.
Article in PLoS genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- An upstream open reading frame represses translation of the neuronal potassium channel KCNQ2.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Expanding the toolbox: Emerging antisense oligonucleotide mechanisms for modulating gene expression.Molecular therapy. Nucleic acids · 2026Review
- Genome-wide detection of human 5' UTR variants that impact protein translation.American journal of human genetics · 2026Article
- Translational buffering tunes gene expression in mice and humans.Genome biology · 2026Article
- Predicted bacterial uRBSs reveal translational coupling and ribosome-mediated RBS occlusion as gene-controlling mechanisms.microLife · 2026Article
- Translation elongation: measurements and applications.RNA biology · 2025Review
- The organization principles of P. falciparum translation initiation features and their potential as drug targets.Nucleic acids research · 2025Article
- Article
- Monosome Stalls the Translation Process Mediated by IGF2BP in Arcuate Nucleus for Puberty Onset Delay.Molecular neurobiology · 2025Article
- Full-length mRNA sequencing resolves novel variation in 5' UTR length for genes expressed during human CD4 T-cell activation.Immunogenetics · 2025Article
- Ubiquitin-dependent translation control mechanisms: Degradation and beyond.Cell reports · 2024Review
- Massively parallel identification of sequence motifs triggering ribosome-associated mRNA quality control.Nucleic acids research · 2024Article
- Ribosome rescue factor PELOTA modulates translation start site choice for C/EBPα protein isoforms.Life science alliance · 2024Article
- Upstream open reading frames: new players in the landscape of cancer gene regulation.NAR cancer · 2024Review
- Translational efficiency in gas-fermenting bacteria: Adding a new layer of regulation to gene expression in acetogens.iScience · 2023Review
- Unlocking the potential of RNA-based therapeutics in the lung: current status and future directions.Frontiers in genetics · 2023Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Upstream open reading frames (uORFs) are present in over half of all human mRNAs. uORFs can potently regulate the translation of downstream open reading frames through several mechanisms: siphoning away scanning ribosomes, regulating re-initiation, and allowing interactions between scanning and elongating ribosomes. However, the consequences of these different mechanisms for the regulation of protein expression remain incompletely understood. Here, we performed systematic measurements on the uORF-containing 5' UTR of the cytomegaloviral UL4 mRNA to test alternative models of uORF-mediated regulation in human cells. We find that a terminal diproline-dependent elongating ribosome stall in the UL4 uORF prevents decreases in main ORF protein expression when ribosome loading onto the mRNA is reduced. This uORF-mediated buffering is insensitive to the location of the ribosome stall along the uORF. Computational kinetic modeling based on our measurements suggests that scanning ribosomes dissociate rather than queue when they collide with stalled elongating ribosomes within the UL4 uORF. We identify several human uORFs that repress main ORF protein expression via a similar terminal diproline motif. We propose that ribosome stalls in uORFs provide a general mechanism for buffering against reductions in main ORF translation during stress and developmental transitions.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.