Deciphering the rules by which 5′-UTR sequences affect protein expression in yeast
2013; National Academy of Sciences; Volume: 110; Issue: 30 Linguagem: Inglês
10.1073/pnas.1222534110
ISSN1091-6490
AutoresShlomi Dvir, Lars Velten, Eilon Sharon, Danny Zeevi, Lucas B. Carey, Adina Weinberger, Eran Segal,
Tópico(s)Genomics and Chromatin Dynamics
ResumoSignificance 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.
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