Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 119, Issue 14, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2112516119
Keywords
uORF; proteome; rare alleles; maize; gene expression
Categories
Funding
- NSF [IOS-1840687, IOS-1822330, IOS-1906619]
- US Department of Agriculture Agricultural Research Service
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The study found that rare variants in the 5' UTR can dysregulate maize protein abundance, and rare variants near the start codon of uORFs can repress or derepress mORF translation. Common variants that modify uORF start codons also disproportionately affect metabolic and whole-plant phenotypes.
The 5' untranslated region (UTR) sequence of eukaryotic mRNAs may contain upstream open reading frames (uORFs), which can regulate translation of the main ORF (mORF). The current model of translational regulation by uORFs posits that when a ribosome scans a mRNA and encounters an 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 maize (Zea mays L.) 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.
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