Photocatalytic Proximity Labeling Maps RNA and Protein Subcellular Landscapes

Mapping the local proteome and transcriptome of specific compartments is crucial for understanding cellular processes but remains challenging. Existing proximity labeling (PL) methods based on enzymes often require genetic manipulation, can suffer from background activity, or are limited to a single molecule type.

Here, we introduce a versatile photocatalytic proximity labeling (PhotoPL) platform using targeted photocatalysts and activatable probes to map both RNA and protein landscapes within defined subcellular regions in living cells. The platform's modular design allows for simple redirection to new targets by chemically conjugating the catalyst to different targeting moieties. Visible light activation of organelle-targeted ruthenium complexes generates localized singlet oxygen or initiates electron transfer, which selectively activates inert phenylselenomethyl phenol probes to generate reactive quinone methide intermediates.