Artigo Acesso aberto Revisado por pares

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

ISSN

1091-6490

Autores

Shlomi Dvir, Lars Velten, Eilon Sharon, Danny Zeevi, Lucas B. Carey, Adina Weinberger, Eran Segal,

Tópico(s)

Genomics and Chromatin Dynamics

Resumo

Significance 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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