RNA-binding proteins and glycoRNAs form domains on the cell surface for cell-penetrating peptide entry

Perr J, Langen A, Almahayni K, Nestola G, Chai P, Lebedenko CG, Volk RF, Detrés D, Caldwell RM, Spiekermann M, Hemberger H, Bisaria N, Aiba T, Sánchez-Rivera FJ, Tzelepis K, Calo E, Möckl L, Zaro BW, Flynn RA (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Cell Elsevier

Book Volume: 188

Pages Range: 1878-1895.e25

Journal Issue: 7

DOI: 10.1016/j.cell.2025.01.040

Abstract

The composition and organization of the cell surface determine how cells interact with their environment. Traditionally, glycosylated transmembrane proteins were thought to be the major constituents of the external surface of the plasma membrane. Here, we provide evidence that a group of RNA-binding proteins (RBPs) is present on the surface of living cells. These cell-surface RBPs (csRBPs) precisely organize into well-defined nanoclusters enriched for multiple RBPs and glycoRNAs, and their clustering can be disrupted by extracellular RNase addition. These glycoRNA-csRBP clusters further serve as sites of cell-surface interaction for the cell-penetrating peptide trans-activator of transcription (TAT). Removal of RNA from the cell surface, or loss of RNA-binding activity by TAT, causes defects in TAT cell internalization. Together, we provide evidence of an expanded view of the cell surface by positioning glycoRNA-csRBP clusters as a regulator of communication between cells and the extracellular environment.

Authors with CRIS profile

Karim Almahayni
Leonhard Möckl

Involved external institutions

University of California San Francisco (UCSF) US United States (USA) (US) Massachusetts Institute of Technology (MIT) US United States (USA) (US) Boston Children's Hospital US United States (USA) (US) Max-Planck-Institut für die Physik des Lichts (MPL) / Max Planck Institute for the Science of Light DE Germany (DE) University of Cambridge GB United Kingdom (GB)

How to cite

APA:

Perr, J., Langen, A., Almahayni, K., Nestola, G., Chai, P., Lebedenko, C.G.,... Flynn, R.A. (2025). RNA-binding proteins and glycoRNAs form domains on the cell surface for cell-penetrating peptide entry. Cell, 188(7), 1878-1895.e25. https://doi.org/10.1016/j.cell.2025.01.040

MLA:

Perr, Jonathan, et al. "RNA-binding proteins and glycoRNAs form domains on the cell surface for cell-penetrating peptide entry." Cell 188.7 (2025): 1878-1895.e25.

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