Programmable sequence-resolved in situ profiling of glycoRNA-protein interactomes by GlycoRNA-Map
- 1Rice University
Abstract
Cell-surface glycoRNAs participate in diverse biological processes, but they were investigated as pooled populations and the protein interactome of individual glycoRNA species remain unresolved. Here we develop GlycoRNA-Map, a programmable photocatalytic proximity-labeling method that maps proteins surrounding sequence-defined endogenous glycoRNAs on living cells. A sialic-acid-binding aptamer and an RNA-hybridization probe jointly recruit a fluorophore-modified oligonucleotide through dual recognition of the glycan and RNA moieties of glycoRNAs. Light-activated biotinylation followed by quantitative mass spectrometry identified 200-418 enriched proteins for each of five glycoRNAs in A549 cells. Comparison of these proteomes revealed limited overlap among different glycoRNA sequences and across cell types, demonstrating that glycoRNA-associated protein environments depend on both RNA identity and cellular context. Transforming growth factor-{beta} receptors 1 and 2 (TGFBR1 and TGFBR2) were identified in the proximal proteomes of multiple glycoRNAs. Removal of cell-surface RNAs enhanced TGF-{beta} receptor signaling and promoted cell migration, demonstrating that glycoRNAs can functionally regulate extracellular signaling by interacting with their protein neighborhoods. GlycoRNA-Map thus provides an accessible strategy for resolving sequence-specific glycoRNA-protein interactome and discovering their roles in membrane signaling.
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BibTeX
@misc{zhang2026programmable,
title = {{Programmable sequence-resolved in situ profiling of glycoRNA-protein interactomes by GlycoRNA-Map}},
author = {X. Zhang and Y. Zhu and K. Baumer and Y. Lu and Y. Fu and J. Liao and X. Shao and Y. Chang and E. Qiao and H. Dong and A. S. Valverde and H.-C. Yeh and S.-H. Chen and H. Renata and Y. Ma},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.29.755375},
url = {https://www.biorxiv.org/content/10.64898/2026.09.29.755375v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Programmable sequence-resolved in situ profiling of glycoRNA-protein interactomes by GlycoRNA-Map
AU - X. Zhang
AU - Y. Zhu
AU - K. Baumer
AU - Y. Lu
AU - Y. Fu
AU - J. Liao
AU - X. Shao
AU - Y. Chang
AU - E. Qiao
AU - H. Dong
AU - A. S. Valverde
AU - H.-C. Yeh
AU - S.-H. Chen
AU - H. Renata
AU - Y. Ma
PY - 2026
DA - 2026/09/29
PB - bioRxiv
DO - 10.64898/2026.09.29.755375
UR - https://www.biorxiv.org/content/10.64898/2026.09.29.755375v1
AB - Cell-surface glycoRNAs participate in diverse biological processes, but they were investigated as pooled populations and the protein interactome of individual glycoRNA species remain unresolved. Here we develop GlycoRNA-Map, a programmable photocatalytic proximity-labeling method that maps proteins surrounding sequence-defined endogenous glycoRNAs on living cells. A sialic-acid-binding aptamer and an RNA-hybridization probe jointly recruit a fluorophore-modified oligonucleotide through dual recognition of the glycan and RNA moieties of glycoRNAs. Light-activated biotinylation followed by quantitative mass spectrometry identified 200-418 enriched proteins for each of five glycoRNAs in A549 cells. Comparison of these proteomes revealed limited overlap among different glycoRNA sequences and across cell types, demonstrating that glycoRNA-associated protein environments depend on both RNA identity and cellular context. Transforming growth factor-{beta} receptors 1 and 2 (TGFBR1 and TGFBR2) were identified in the proximal proteomes of multiple glycoRNAs. Removal of cell-surface RNAs enhanced TGF-{beta} receptor signaling and promoted cell migration, demonstrating that glycoRNAs can functionally regulate extracellular signaling by interacting with their protein neighborhoods. GlycoRNA-Map thus provides an accessible strategy for resolving sequence-specific glycoRNA-protein interactome and discovering their roles in membrane signaling.
ER -