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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article numbere1004407
JournalPLoS Genetics
Volume10
Issue number6
DOIs
StatePublished - 26 Jun 2014

All Science Journal Classification (ASJC) codes

  • Genetics(clinical)
  • Genetics
  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Cancer Research

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