RNA on Display: Cell Surface RNA as a Novel Layer of Cellular Regulation

Serina Chahal; Pious Jose; Adam Greasley; Kevin Vytlingam; Raj Kumar Thapa; Hayley Pyne; Amal Abu Omar; Xiufen Zheng

doi:10.34133/research.1147

RNA on Display: Cell Surface RNA as a Novel Layer of Cellular Regulation

Research (Wash D C). 2026 Feb 27:9:1147. doi: 10.34133/research.1147. eCollection 2026.

Authors

Serina Chahal¹, Pious Jose², Adam Greasley², Kevin Vytlingam², Raj Kumar Thapa³, Hayley Pyne¹, Amal Abu Omar^{3

4}, Xiufen Zheng^{1

2

3

5

6}

Affiliations

¹ Department of Microbiology and Immunology, Western University, London, ON, Canada.
² Department of Pathology and Laboratory Medicine, Western University, London, ON, Canada.
³ Department of Surgery, Western University, London, ON, Canada.
⁴ Department of Physiology and Biochemistry, Jordan University of Science and Technology, Irbid, Jordan.
⁵ The Multi-Organ Transplant Program, London Health Sciences Center Research Institute, London, ON, Canada.
⁶ Matthew Mailing Center for Translational Transplant Studies, London Health Sciences Center, London, ON, Canada.

Abstract

RNA has been established as an essential molecule in virtually all cellular processes. Besides its role in cellular modulation via extracellular vesicular release, it has long been thought to only exert its function intracellularly. Recent discoveries have shown evidence of extracellular RNA tethered to the cell surface of different cell types. These cell surface RNAs are predominantly modified with sialylated glycans, denominating them cell surface glycoRNAs. While the expression of cell surface glycoRNAs has been found on a wide array of immune cell and cancer cell types, research on its functional roles has only recently been explored due to challenges in detection, isolation, and sequencing of this new subclass of RNA. In this review, the history, biogenesis, detection and isolation techniques, and functional roles of cell surface RNA to date will be discussed, in addition to commenting on its translational capacity for studying immunomodulation and disease. Acknowledging the presence of cell surface RNAs and propelling our understanding on their function will provide a new avenue to study cellular modulation and cell-cell communication.

Publication types

Review