ArticleProceedings of the National Academy of Sciences of the United States of America2013
Deciphering the rules by which 5'-UTR sequences affect protein expression in yeast.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 149 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
149 citing papers in PubMed, 282 citations in OpenAlex.
- Modular synthetic cross-kingdom promoters enable coordinated expression in Escherichia coli and Saccharomyces cerevisiae.Nucleic acids research · 2026Article
- Heat stress promotes pre-tRNA capping to modulate cap-dependent translation in Saccharomyces cerevisiae.Nature communications · 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
- Multi-Tissue Omics Analysis Uncovers Translational Regulation Underlying Complex Traits in Pigs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- UTR-DynaPro: a CNN-transformer multimodal language model for decoding 5'UTR regulatory mechanisms.Scientific reports · 2026Article
- A synthetic ERFVII-dependent circuit in yeast sheds light on the regulation of early hypoxic responses of plants.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Omics-Based Expression Cassette for Heterologous Protein Production inACS synthetic biology · 2026Article
- Inferring fungal cis-regulatory networks from genome sequences via unsupervised and interpretable representation learning.Genetics · 2026Article
- The patterns of alternative TSS usage explain the highly heterogeneous landscape of 5'UTR lengths in eukaryotes.NAR genomics and bioinformatics · 2025Article
- Control of gene output by intron RNA structure.bioRxiv : the preprint server for biology · 2025Article
- Combining QTL mapping and RNA-Seq reveals candidate genes controlling flag leaf width in foxtail millet.BMC plant biology · 2025Article
- The generation and consequences of N-terminal proteoform diversity.Cell reports · 2025Review
- Human Synthetic Biology and Programmable Gene Regulation Control.Annual review of genomics and human genetics · 2025Review
- Article
- The regulatory landscape of 5' UTRs in translational control during zebrafish embryogenesis.Developmental cell · 2025Article
- Deciphering the landscape of cis-acting sequences in natural yeast transcript leaders.Nucleic acids research · 2025Article
- NaP-TRAP reveals the regulatory grammar in 5'UTR-mediated translation regulation during zebrafish development.Nature communications · 2024Article
- Designing strong inducible synthetic promoters in yeasts.Nature communications · 2024Article
- Decoding biology with massively parallel reporter assays and machine learning.Genes & development · 2024Review
- High-throughput identification of functional regulatory SNPs in systemic lupus erythematosus.Nature communications · 2024Article
89 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 2 institutions in 3 countries.
Funding
Abstract
The 5'-untranslated region (5'-UTR) of mRNAs contains elements that affect expression, yet the rules by which these regions exert their effect are poorly understood. Here, we studied the impact of 5'-UTR sequences on protein levels in yeast, by constructing a large-scale library of mutants that differ only in the 10 bp preceding the translational start site of a fluorescent reporter. Using a high-throughput sequencing strategy, we obtained highly accurate measurements of protein abundance for over 2,000 unique sequence variants. The resulting pool spanned an approximately sevenfold range of protein levels, demonstrating the powerful consequences of sequence manipulations of even 1-10 nucleotides immediately upstream of the start codon. We devised computational models that predicted over 70% of the measured expression variability in held-out sequence variants. Notably, a combined model of the most prominent features successfully explained protein abundance in an additional, independently constructed library, whose nucleotide composition differed greatly from the library used to parameterize the model. Our analysis reveals the dominant contribution of the start codon context at positions -3 to -1, mRNA secondary structure, and out-of-frame upstream AUGs (uAUGs) to phenotypic diversity, thereby advancing our understanding of how protein levels are modulated by 5'-UTR sequences, and paving the way toward predictably tuning protein expression through manipulations of 5'-UTRs.
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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.