Predictable control of RNA lifetime using engineered degradation-tuning RNAs

Qi Zhang, Duo Ma, Fuqing Wu, Kylie Standage-Beier, Xingwen Chen, Kaiyue Wu, Alexander Green, Xiao Wang

Research output: Contribution to journalArticlepeer-review

Abstract

The ability to tune RNA and gene expression dynamics is greatly needed for biotechnological applications. Native RNA stabilizers or engineered 5′ stability hairpins have been used to regulate transcript half-life to control recombinant protein expression. However, these methods have been mostly ad hoc and hence lack predictability and modularity. Here, we report a library of RNA modules called degradation-tuning RNAs (dtRNAs) that can increase or decrease transcript stability in vivo and in vitro. dtRNAs enable modulation of transcript stability over a 40-fold dynamic range in Escherichia coli with minimal influence on translation initiation. We harness dtRNAs in messenger RNAs and noncoding RNAs to tune gene circuit dynamics and enhance CRISPR interference in vivo. Use of stabilizing dtRNAs in cell-free transcription-translation reactions also tunes gene and RNA aptamer production. Finally, we combine dtRNAs with toehold switch sensors to enhance the performance of paper-based norovirus diagnostics, illustrating the potential of dtRNAs for biotechnological applications. [Figure not available: see fulltext.].

Original languageEnglish (US)
Pages (from-to)828-836
Number of pages9
JournalNature Chemical Biology
Volume17
Issue number7
DOIs
StatePublished - Jul 2021

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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