ArticleThe EMBO journal2016
Upstream ORFs are prevalent translational repressors in vertebrates.
Article in The EMBO journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 239 papers.
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Who cites it
239 citing papers in PubMed, 382 citations in OpenAlex.
- Global translational reprogramming inVirulence · 2026Article
- Real-time single-molecule imaging in zebrafish embryos uncovers noncanonical translation.Science advances · 2026Article
- Integrated Transcriptomic Analysis of Skin Pigmentation Development inInternational journal of molecular sciences · 2026Article
- PKD1 upstream open reading frames affect Polycystin-1 expression and polycystic kidney disease phenotypes.The Journal of clinical investigation · 2026Article
- Ribo-ITP enables identification of translons from limited input samples.Nature communications · 2026Article
- Overlapping upstream ORFs repress translation and expand proteome diversity in Arabidopsis.bioRxiv : the preprint server for biology · 2026Article
- An SLCO2B1 mRNA Isoform Acts as a Noncoding RNA to Drive Cancer Progression by Triggering Protein Biosynthesis.Cancer research · 2026Article
- Cell type-specific expression and subcellular localization of the human insulin upstream open reading frame (INSU) protein in pancreatic β-cells.The Journal of biological chemistry · 2026Article
- NaP-TRAP: A Versatile and Accessible Workflow to Dissect Principles of Translational Regulation and mRNA Stability.Current protocols · 2026Article
- A-to-I RNA editing remodels 5'-UTR initiation codons to tune translational output.Scientific reports · 2026Article
- The role of FMR1 mRNA structure on the efficiency of non-canonical translation of toxic polyglycine protein.Nucleic acids research · 2026Article
- Identification of conserved RNA regulatory switches in living cells using RNA secondary structure ensemble mapping and covariation analysis.Nature biotechnology · 2026Article
- Unlocking translational control of specialized metabolism in plants through 5'UTR structure.Science advances · 2026Article
- CRISPR-Cas9-mediated uATG introduction in the 5'UTR of the Uox gene for hyperuricemia mouse models: implications for gout and metabolic disorders.Science China. Life sciences · 2026Article
- NaP-TRAP: A versatile and accessible workflow to dissect principles of translational regulation and mRNA stability.bioRxiv : the preprint server for biology · 2026Article
- Multi-Tissue Omics Analysis Uncovers Translational Regulation Underlying Complex Traits in Pigs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A microscopy-based CRISPR screening platform enables organellar functional genomics and illuminates ciliary biology.Developmental cell · 2026Article
- Extended Shine-Dalgarno motifs govern translation initiation in Staphylococcus aureus.Nature communications · 2026Article
- PKD1 5'UTR variants are a rare cause of disease in ADPKD and suggest a new focus for therapeutic development.European journal of human genetics : EJHG · 2026Article
- Integrated analysis of post-transcriptional regulations reveals insights into acute myeloid leukemia.Communications biology · 2025Article
179 more citing papers are in PubMed but not listed here.
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3 authors at 1 institution in 1 country.
Funding
Abstract
Regulation of gene expression is fundamental in establishing cellular diversity and a target of natural selection. Untranslated mRNA regions (UTRs) are key mediators of post-transcriptional regulation. Previous studies have predicted thousands of ORFs in 5'UTRs, the vast majority of which have unknown function. Here, we present a systematic analysis of the translation and function of upstream open reading frames (uORFs) across vertebrates. Using high-resolution ribosome footprinting, we find that (i)uORFs are prevalent within vertebrate transcriptomes, (ii) the majority show signatures of active translation, and (iii)uORFs act as potent regulators of translation and RNA levels, with a similar magnitude to miRNAs. Reporter experiments reveal clear repression of downstream translation by uORFs/oORFs. uORF number, intercistronic distance, overlap with the CDS, and initiation context most strongly influence translation. Evolution has targeted these features to favor uORFs amenable to regulation over constitutively repressive uORFs/oORFs. Finally, we observe that the regulatory potential of uORFs on individual genes is conserved across species. These results provide insight into the regulatory code within mRNA leader sequences and their capacity to modulate translation across vertebrates.
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Registered trials
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.