| Autor: |
Hunt VM; Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE, USA. wilfred@udel.edu., Chen W; Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE, USA. wilfred@udel.edu. |
| Jazyk: |
angličtina |
| Zdroj: |
Chemical communications (Cambridge, England) [Chem Commun (Camb)] 2022 May 24; Vol. 58 (42), pp. 6215-6218. Date of Electronic Publication: 2022 May 24. |
| DOI: |
10.1039/d2cc01478e |
| Abstrakt: |
To 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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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