Open AccessPredictable control of RNA lifetime using engineered degradation-tuning RNAs
Author(s) -
Qi Zhang,
Duo Ma,
Fuqing Wu,
Kylie Standage-Beier,
Xingwen Chen,
Kaiyue Wu,
Alexander A. Green,
Xiao Wang
Publication year - 2021
Publication title -
nature chemical biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.412
H-Index - 216
eISSN - 1552-4469
pISSN - 1552-4450
DOI - 10.1038/s41589-021-00816-4
Subject(s) - rna , rna interference , biology , crispr , synthetic biology , computational biology , translation (biology) , trans activating crrna , transcription (linguistics) , gene expression , microbiology and biotechnology , messenger rna , dna directed rna interference , cas9 , gene , genetics , linguistics , philosophy
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.