DOI: 10.1101/501767Dec 19, 2018Paper

De novo Design of Translational RNA Repressors

BioRxiv : the Preprint Server for Biology
Paul D CarlsonJulius Lucks

Abstract

A central goal of synthetic biology is the development of methods for the predictable control of gene expression. RNA is an attractive substrate by which to achieve this goal because the relationship between its sequence, structure, and function is being uncovered with increasing depth. In addition, design approaches that use this relationship are becoming increasingly effective, as evidenced by significant progress in the de novo design of RNA-based gene regulatory mechanisms that activate transcription and translation in bacterial cells. However, the design of synthetic RNA mechanisms that are efficient and versatile repressors of gene expression has lagged, despite their importance for gene regulation and genetic circuit construction. We address this gap by developing two new classes of RNA regulators, toehold repressors and looped antisense oligonucleotides (LASOs), that repress translation of a downstream gene in response to an arbitrary input RNA sequence. Characterization studies show that these designed RNAs robustly repress translation, are highly orthogonal, and can be multiplexed with translational activators. We show that our LASO design can repress endogenous mRNA targets and distinguish between closely-related gen...Continue Reading

Related Concepts

Gene Expression
Genes
Genes, Regulator
Repressor Proteins
RNA
RNA, Messenger
Oligonucleotides, Antisense
Transcriptional Activation
Protein Biosynthesis
Structure

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