Figure 1.
Optochemical regulation of splice switching with the LASSO for an OFF → ON gene expression light switch. Schematics for the two RNA splicing pathways (black) and the mutant intron (red) are shown. (A) In the absence of irradiation, the LASSO does not bind to the target site due to inhibition of base hybridization from the nucleobase caging groups. (B) UV decaging of the LASSO enables conditional splice correction of the aberrant mutant intron and activation of gene expression. (C) Dark blue boxes represent 2′OMe-NPOM-caged uridine residues, with the light-removable group indicated in red. (D) HeLa:EGFP654 cells were transfected with the LASSO, irradiated for 2 min or kept in the dark, and imaged for EGFP expression after 24 h. Images of the EGFP channel (left) and the EGFP channel merged with a brightfield image (right) are shown. Scale bars indicate 0.2 mm.