A portable regulatory RNA array design enables tunable and complex regulation across diverse bacteria

A lack of composable and tunable gene regulators has hindered efforts to engineer non-model bacteria and consortia. Toward addressing this, we explore the broad-host potential of small transcription activating RNA (STAR) and propose a design strategy to achieve tunable gene control. First, we demons...

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Bibliographic Details
Published in:Nature communications 2023-08, Vol.14 (1), p.5268-5268, Article 5268
Main Authors: Liu, Baiyang, Samaniego, Christian Cuba, Bennett, Matthew R., Franco, Elisa, Chappell, James
Format: Article
Language:English
Subjects:
38/35
49/23
631/553/552
631/92/552
Arrays
Artificial neural networks
Bacteria
Bacteria - genetics
Bacteriophages - genetics
Consortia
Design
DNA-directed RNA polymerase
E coli
Engineering
Engineers
Escherichia coli - genetics
Gene expression
Humanities and Social Sciences
multidisciplinary
Multiplexing
Neural networks
Portability
Ribonucleic acid
RNA
RNA phages
RNA polymerase
Science
Science (multidisciplinary)
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Summary:A lack of composable and tunable gene regulators has hindered efforts to engineer non-model bacteria and consortia. Toward addressing this, we explore the broad-host potential of small transcription activating RNA (STAR) and propose a design strategy to achieve tunable gene control. First, we demonstrate that STARs optimized for E. coli function across different Gram-negative species and can actuate using phage RNA polymerase, suggesting that RNA systems acting at the level of transcription are portable. Second, we explore an RNA design strategy that uses arrays of tandem and transcriptionally fused RNA regulators to precisely alter regulator concentration from 1 to 8 copies. This provides a simple means to predictably tune output gain across species and does not require access to large regulatory part libraries. Finally, we show RNA arrays can be used to achieve tunable cascading and multiplexing circuits across species, analogous to the motifs used in artificial neural networks. A lack of composable and tunable gene regulators has hindered efforts to engineer nonmodel bacteria and consortia. Here the authors deliver a tunable gene regulatory platform based on RNA arrays to control gene expression across different microbes.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-023-40785-x