title: Accurate, model-based tuning of synthetic gene expression using introns in S. cerevisiae.
abstract: 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.
authors: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors: Ido
authors: I
authors: Yofe
authors: Department of Biomedical Engineering, Tel-Aviv University, Tel Aviv, Israel.
authors: Zohar
authors: Z
authors: Zafrir
authors: Department of Applied Mathematics and Computer Science, and Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel.
authors: Rachel
authors: R
authors: Blau
authors: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors: Maya
authors: M
authors: Schuldiner
authors: Department of Biomedical Engineering, Tel-Aviv University, Tel Aviv, Israel; The Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel.
authors: Tamir
authors: T
authors: Tuller
authors: Department of Applied Mathematics and Computer Science, and Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel.
authors: Ehud
authors: E
authors: Shapiro
authors: Department of Applied Mathematics and Computer Science, and Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel.
authors: Tuval
authors: T
authors: Ben-Yehezkel
mesh_terms: D001426:Bacterial Proteins; D015966:Gene Expression Regulation, Fungal; D005813:Genes, Synthetic / Q000235:genetics*; D005818:Genetic Engineering; D007438:Introns / Q000235:genetics*; D008164:Luminescent Proteins; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D012441:Saccharomyces cerevisiae
chemical_list: D001426:Bacterial Proteins; D008164:Luminescent Proteins; C054562:yellow fluorescent protein, Bacteria