A unified photosensitizer platform for <i>in situ</i> DNA-, RNA-, and protein-directed proximity labeling

hybridization workflows to specifically target organic fluorophore photosensitizers to intracellular targets for proximity labeling in fixed cells. POCA-targeted proximity labeling requires minimal cellular input and does not require genetic engineering. Additionally, POCA photosensitizers are selected to also be fluorescent, enabling direct confirmation of on-target localization by imaging prior to proteomic analysis. To demonstrate broad utility, we apply POCA across multiple molecular targets spanning protein, RNA, and genomic DNA, including components of the nuclear pore complex, nucleolus, nuclear speckles, telomeres, and pericentromeric heterochromatin. By anchoring proximity labeling to both a protein and an RNA within the same nuclear compartment, we resolve shared and distinct proximal proteomes from orthogonal molecular perspectives.

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Publication Details

Journal
bioRxiv (Cold Spring Harbor Laboratory)
Published
2026-05-01
DOI
https://doi.org/10.64898/2026.04.30.721698
Primary Topic
Biotin and Related Studies
Type
article
Field-Weighted Citation Impact
0.00

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article

A unified photosensitizer platform for in situ DNA-, RNA-, and protein-directed proximity labeling

Brian J. Beliveau, Luke D. Lavis, Jonathan B. Grimm, Kyle Brandt et al.
bioRxiv (Cold Spring Harbor Laboratory)
Biotin and Related Studies
article

A unified photosensitizer platform for in situ DNA-, RNA-, and protein-directed proximity labeling

Brian J. Beliveau, Luke D. Lavis, Jonathan B. Grimm, Kyle Brandt, Edward L. Huttlin, Devin K. Schweppe, Conor P. Herlihy, Olivia Weissenfels, Mary Krebs, Nicolas J Longhi, Hanna Goldberg, Conor J Kelly, Keriann M Backus, Lidan Li, Elijah B Biletch
article en

Abstract

hybridization workflows to specifically target organic fluorophore photosensitizers to intracellular targets for proximity labeling in fixed cells. POCA-targeted proximity labeling requires minimal cellular input and does not require genetic engineering. Additionally, POCA photosensitizers are selected to also be fluorescent, enabling direct confirmation of on-target localization by imaging prior to proteomic analysis. To demonstrate broad utility, we apply POCA across multiple molecular targets spanning protein, RNA, and genomic DNA, including components of the nuclear pore complex, nucleolus, nuclear speckles, telomeres, and pericentromeric heterochromatin. By anchoring proximity labeling to both a protein and an RNA within the same nuclear compartment, we resolve shared and distinct proximal proteomes from orthogonal molecular perspectives.

bioRxiv (Cold Spring Harbor Laboratory)
Howard Hughes Medical Institute (US), Harvard University (US), University of California, Los Angeles (US), California Institute for Regenerative Medicine (US), Janelia Research Campus (US), University of Washington (US), Brotman Baty Institute (US)
National Institutes of Health
Openalex Percentile: Top 12%
Biotin and Related Studies
DOIOpen Access PDFOpenAlex
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