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

## TL;DR

This paper reviews recent discoveries about RNA found on the surface of cells and its potential role in cellular communication and disease.

## Contribution

The paper introduces cell surface glycoRNAs as a novel regulatory layer and summarizes recent advances in their detection and function.

## Key findings

- Cell surface RNAs are modified with sialylated glycans and found on immune and cancer cells.
- Recent techniques have enabled detection and isolation of cell surface glycoRNAs.
- Cell surface RNA may offer new insights into immunomodulation and disease mechanisms.

## 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.