RNA-responsive elements for eukaryotic translational control

The ability to control translation of endogenous or exogenous RNAs in eukaryotic cells would facilitate a variety of biotechnological applications. Current strategies are limited by low fold changes in transgene output and the size of trigger RNAs (trRNAs). Here we introduce eukaryotic toehold switc...

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Bibliographic Details
Published in:Nature biotechnology 2022-04, Vol.40 (4), p.539-545
Main Authors: Zhao, Evan M, Mao, Angelo S, de Puig, Helena, Zhang, Kehan, Tippens, Nathaniel D, Tan, Xiao, Ran, F Ann, Han, Isaac, Nguyen, Peter Q, Chory, Emma J, Hua, Tiffany Y, Ramesh, Pradeep, Thompson, David B, Oh, Crystal Yuri, Zigon, Eric S, English, Max A, Collins, James J
Format: Article
Language:English
Subjects:
Animals
Annealing
Gene expression
Internal ribosome entry site
Mammalian cells
Mammals - genetics
Optimization
Protein Biosynthesis - genetics
Ribonucleic acid
RNA
RNA, Viral - genetics
Switches
Transgenes
Translation
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Summary:The ability to control translation of endogenous or exogenous RNAs in eukaryotic cells would facilitate a variety of biotechnological applications. Current strategies are limited by low fold changes in transgene output and the size of trigger RNAs (trRNAs). Here we introduce eukaryotic toehold switches (eToeholds) as modular riboregulators. eToeholds contain internal ribosome entry site sequences and form inhibitory loops in the absence of a specific trRNA. When the trRNA is present, eToeholds anneal to it, disrupting the inhibitory loops and allowing translation. Through optimization of RNA annealing, we achieved up to 16-fold induction of transgene expression in mammalian cells. We demonstrate that eToeholds can discriminate among viral infection status, presence or absence of gene expression and cell types based on the presence of exogenous or endogenous RNA transcripts.
ISSN:1087-0156
1546-1696
DOI:10.1038/s41587-021-01068-2