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ARS Home » Northeast Area » Ithaca, New York » Robert W. Holley Center for Agriculture & Health » Plant, Soil and Nutrition Research » Research » Publications at this Location » Publication #396648

Research Project: Improving Crop Efficiency Using Genomic Diversity and Computational Modeling

Location: Plant, Soil and Nutrition Research

Title: Variation in upstream open reading frames contributes to allelic diversity in maize protein abundance

item GAGE, JOSEPH - North Carolina State University
item MALI, SUJINA - Washington University
item MCLOUGHLIN, FIONN - Washington University
item KHAIPHO-BURCH, MERRITT - Cornell University
item MONIER, BRANDON - Cornell University
item BAILEY-SERRES, JULIA - University Of California, Riverside
item VIERSTRA, RICHARD - Washington University
item Buckler, Edward - Ed

Submitted to: Proceedings of the National Academy of Sciences (PNAS)
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/22/2022
Publication Date: 3/29/2022
Citation: Gage, J.L., Mali, S., McLoughlin, F., Khaipho-Burch, M., Monier, B., Bailey-Serres, J., Vierstra, R.D., Buckler IV, E.S. 2022. Variation in upstream open reading frames contributes to allelic diversity in maize protein abundance. Proceedings of the National Academy of Sciences (PNAS). 119(14). Article e2112516119.

Interpretive Summary: We know that genetic differences between individuals can cause apparent physical differences. In many cases, those physical differences are caused by different levels of gene expression. What is still unclear, however, are the mechanisms by which genetic differences cause differing levels of gene expression across the genome. One specific mechanism of regulating gene expression (called “upstream open reading frames”; “uORFs”) has been discovered in limited cases and highly controlled experiments, but we do not know the extent to which it influences differences between natural populations of crop plants. We show that genetic variation can alter the function of uORFs and cause changes in gene expression. We also show that genetic variation which alters uORF function is important for physical differences between individuals. This work allows us to identify a small set of genetic variation that has large effects on gene expression and physical differences between individuals. We can consider about 5,000x less genetic variation when searching for causes of different gene expression between individuals. Because there is so much genetic variation between individuals, reducing the search space dramatically is helpful for building targeted models that predict plant performance, and may also be of use for identifying targets for gene editing or genome engineering.

Technical Abstract: 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.