A microRNA-gated thgRNA platform for multiplexed activation of gene expression in mammalian cells

Simple item page
Author(s)Hunt, Victoria M.
Author(s)Chen, Wilfred
Date Accessioned2022-05-27T17:52:13Z
Date Available2022-05-27T17:52:13Z
Publication Date2022-04-26
DescriptionThis article was originally published in Chemical Communications. The version of record is available at: https://doi.org/10.1039/D2CC01478E. This article will be embargoed until 04/26/2023.en_US
AbstractTo effectively reprogram cellular regulatory networks towards desired phenotypes, it is critical to have the ability to provide precise gene regulation in a spatiotemporal manner. We have previously engineered toehold-gated guide RNA (thgRNA) to enable conditional activation of dCas9-mediated transcriptional upregulation in mammalian cells using synthetic RNA triggers. Here, we demonstrate that microRNA (miR)-gated thgRNAs can be transcribed by type II RNA polymerase to allow multiplexed transcriptional activation using both mRNA and miR. Activation is achieved only by proper miR-mediated processing of the flanking 5′ cap and 3′ poly A tail and hairpin unblocking by mRNA via strand displacement. This new AND-gate design is exploited to elicit conditional protein degradation based on induced expression of a specific ubiquibody. This new strategy may find many new applications in an RNA-responsive manner.en_US
SponsorWe would like to acknowledge the funding support from NSF (MCB2013991, MCB 1817675, and CBE1803008).en_US
CitationHunt, Victoria M., and Wilfred Chen. 2022. “A MicroRNA-Gated ThgRNA Platform for Multiplexed Activation of Gene Expression in Mammalian Cells.” Chemical Communications 58 (42): 6215–18. https://doi.org/10.1039/D2CC01478E.en_US
ISSN1364-548X
URLhttps://udspace.udel.edu/handle/19716/30910
Languageen_USen_US
PublisherChemical Communicationsen_US
TitleA microRNA-gated thgRNA platform for multiplexed activation of gene expression in mammalian cellsen_US
TypeArticleen_US
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
A microRNA-gated thgRNA platform for multiplexed.pdf
Size:
1.1 MB
Format:
Adobe Portable Document Format
Description:
Main article
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
2.22 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Open Access Publications