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RNA-responsive elements for eukaryotic translational control

delete2021-10-28
delete50
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OA
AI
E
Evan M. Zhao
A
Angelo S. Mao
H
Helena de Puig
K
Kehan Zhang
N
Nathaniel D. Tippens
X
Xiao Tan
F
Fanlei Ran
I
Isaac Han
P
Peter Q. Nguyen
E
Emma J. Chory
T
Tiffany Y. Hua
P
Pradeep Ramesh
D
David B. Thompson
C
Crystal Yuri Oh
E
Eric Zigon
M
Max A. English
J
James J. Collins *
DOI:10.1038/s41587-021-01068-2delete
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Abstract

Abstract

En 中文
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. The translation of transgenes is regulated using RNA sensors.
Keywords:
INTERNAL RIBOSOME ENTRY
INFLUENZA-A VIRUS
SITE IRES
INITIATION
TRANSCRIPTION
SWITCHES
PROMOTER
BINDING

Journal

Nature Biotechnology cover
Nature Biotechnology
IF:
41.7
Papers:
1.2W
Citations:
10.1W

Organization

H
Harvard University
Scholars:
26.5W
Papers: 22.0W
Citations: 28.7W