Variation in upstream open reading frames contributes to allelic diversity in protein abundance
Gage, J. L.; Mali, S.; McLoughlin, F.; Khaipho-Burch, M.; Monier, B.; Bailey-Serres, J.; Vierstra, R. D.; Buckler, E. S.
Show abstract
The 5 untranslated region (UTR) sequence of eukaryotic mRNAs may contain upstream open reading frames (uORFs), which can regulate translation of the main open reading frame (mORF). The current model of translational regulation by uORFs posits that when a ribosome scans an mRNA and encounters a uORF, translation of that uORF can prevent ribosomes from reaching the mORF and cause decreased mORF translation. In this study, we first observed that rare variants in the 5 UTR dysregulate protein abundance. Upon further investigation, we found that rare variants near the start codon of uORFs can repress or derepress mORF translation, causing allelic changes in protein abundance. This finding holds for common variants as well, and common variants that modify uORF start codons also contribute disproportionately to metabolic and whole-plant phenotypes, suggesting that translational regulation by uORFs serves an adaptive function. These results provide evidence for the mechanisms by which natural sequence variation modulates gene expression, and ultimately, phenotype.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- ZmPILS6 is an auxin efflux carrier required for maize root morphogenesis 96%
- Recruitment of an ancient branching program to suppress carpel development in maize flowers 95%
- ENHANCED GRAVITROPISM 2 encodes a STERILE ALPHA MOTIVE containing protein that controls root growth angle in barley and wheat 95%
Similar papers in this journal
- Gene disruption by structural mutations drives selection in US rice breeding over the last century 94%
- Functional mapping of N-terminal residues in the yeast proteome uncovers novel determinants for mitochondrial protein import. 94%
- Evolutionarily conserved non-protein-coding regions in the chicken genome harbor functionally important variation 93%
Similar papers in this journal
- The cis-regulatory codes of response to combined heat and drought stress in Arabidopsis thaliana 94%
- Inferring gene-pathway associations from consolidated transcriptome datasets: an interactive gene network explorer for Tetrahymena thermophila 94%
- DiffSegR: An RNA-Seq data driven method for differential expression analysis using changepoint detection 93%
Similar papers in this journal
- Identification of essential genes and fluconazole resistance genes in Candida glabrata by profiling of Hermes transposon insertions. 94%
- High-throughput identification of nuclear envelope protein interactions in Schizosaccharomyces pombe using an arrayed membrane yeast-two hybrid library 93%
- Analyses of Mutational Patterns Induced by Formaldehyde and Acetaldehyde Reveal Similarity to a Common Mutational Signature 91%
Similar papers in this journal
- Refining the transcriptome of the human malaria parasite Plasmodium falciparum using amplification-free RNA-seq 93%
- Expert Curation of the Human and Mouse Olfactory Receptor Gene Repertoires Identifies Conserved Coding Regions Split Across Two Exons 92%
- Identification and prediction of developmental enhancers in sea urchin embryos 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.