Deciphering the rules by which 5′-UTR sequences affect protein expression in yeast
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- Shlomi Dvir
- Departments of aComputer Science and Applied Mathematics and
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- Lars Velten
- Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany
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- Eilon Sharon
- Departments of aComputer Science and Applied Mathematics and
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- Danny Zeevi
- Departments of aComputer Science and Applied Mathematics and
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- Lucas B. Carey
- Departments of aComputer Science and Applied Mathematics and
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- Adina Weinberger
- Departments of aComputer Science and Applied Mathematics and
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- Eran Segal
- Departments of aComputer Science and Applied Mathematics and
書誌事項
- 公開日
- 2013-07-05
- DOI
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- 10.1073/pnas.1222534110
- 公開者
- Proceedings of the National Academy of Sciences
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説明
<jats:title>Significance</jats:title><jats:p>This study quantifies how protein levels are determined by the underlying 5′-UTR sequence of an mRNA. We accurately measured protein abundance in 2,041 5′-UTR sequence variants, differing only in positions −10 to −1. We show that a few nucleotide substitutions can significantly alter protein expression. We also developed a predictive model that explains two-thirds of the expression variation. We provide convincing evidence that key regulatory elements, including AUG sequence context, mRNA secondary structure, and out-of-frame upstream AUGs conjointly modulate protein levels. Our study can aid in synthetic biology applications, by suggesting sequence manipulations for fine-tuning protein expression in a predictable manner.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 110 (30), E2792-, 2013-07-05
Proceedings of the National Academy of Sciences
