Light-Activated Control of Translation by Enzymatic Covalent mRNA Labeling.
Angew Chem Int Ed Engl
; 57(11): 2822-2826, 2018 03 05.
Article
en En
| MEDLINE
| ID: mdl-29380476
ABSTRACT
Activation of cellular protein expression upon visible-light photocleavage of small-molecule caging groups covalently attached to the 5'â
untranslated region (5'â
UTR) of an mRNA was achieved. These photocleavable caging groups are conjugated to inâ
vitro transcribed mRNA (IVT-mRNA) through RNA transglycosylation, an enzymatic process in which a bacterial tRNA guanine transglycosylase (TGT) exchanges a guanine nucleobase in a specific 17-nucleotide motif (Tag) for synthetic pre-queuosine1 (preQ1 ) derivatives. The caging groups severely reduce mRNA translation efficiency when strategically placed in the 5' UTR. Using this method, we demonstrate the successful spatiotemporal photoregulation of gene expression with single-cell precision. Our method can be applied to therapeutically relevant chemically modified mRNA (mod-mRNA) transcripts. This strategy provides a modular and efficient approach for developing synthetic gene regulatory circuits, biotechnological applications, and therapeutic discovery.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Biosíntesis de Proteínas
/
ARN Mensajero
/
Optogenética
Límite:
Humans
Idioma:
En
Año:
2018
Tipo del documento:
Article