Journal Article

Accurate, Model-Based Tuning of Synthetic Gene Expression Using Introns in S. cerevisiae

Tuller, Tamir, Ben-Yehezkel, Tuval, Zafrir, Zohar, Yofe, Ido, Shapiro, Ehud, Blau, Rachel, Schuldiner, Maya

2014

Overview

Introns are key regulators of eukaryotic gene expression and present a potentially powerful tool for the design of synthetic eukaryotic gene expression systems. However, intronic control over gene expression is governed by a multitude of complex, incompletely understood, regulatory mechanisms. Despite this lack of detailed mechanistic understanding, here we show how a relatively simple model enables accurate and predictable tuning of synthetic gene expression system in yeast using several predictive intron features such as transcript folding and sequence motifs. Using only natural Saccharomyces cerevisiae introns as regulators, we demonstrate fine and accurate control over gene expression spanning a 100 fold expression range. These results broaden the engineering toolbox of synthetic gene expression systems and provide a framework in which precise and robust tuning of gene expression is accomplished.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Bacterial Proteins / Binding sites / Biology and Life Sciences / Efficiency / Engineering and Technology / Eukaryotes / Gene expression / Gene Expression Regulation, Fungal / Genes, Synthetic - genetics / Genetic aspects / Genetic Engineering / Growth rate / Introns - genetics / Libraries / Luminescent Proteins / Regulatory Sequences, Nucleic Acid - genetics / Saccharomyces cerevisiae / Synthetic biology