# Mechanisms and functions of cell surface glycoRNAs

> **NIH NIH R35** · BOSTON CHILDREN'S HOSPITAL · 2024 · $442,500

## Abstract

PROJECT SUMMARY/ ABSTRACT
The cell surface is a platform for physical and regulatory control over cell biology, positioning it to be a key
interface for diagnostic targeting and therapeutic intervention. While RNA is a central polymer in biology most
thought and experimental effort devoted to RNA biology has been confined to intracellular spaces and excluded
from participating in cell surface biology. On the cell surface, carbohydrate polymers (glycans) are of critical
importance due to biophysical and signaling activities. Interestingly, despite both polymers playing central roles
in biology, RNA and glycans have largely existed in entirely non-overlapping fields of study. However, my work
has provided evidence of a hybrid molecule, an RNA-glycan conjugate (glycoRNA); this new class of biomolecule
represents a direct link between RNA and glycobiology. Critically, glycoRNAs are localized to the external
surface of living cells and can engage with immunomodulatory Siglec receptors. Thus, glycoRNAs are positioned
on a surface of critical regulatory importance, with access to cell-cell interactions, pathogens, and signaling
receptors on the cell surface. However, we currently lack facile tools to study this new cell surface molecule, we
do not understand the molecular or atomic composition of glycoRNAs, and we have a poor understanding of
how many species biosynthesize glycoRNAs. This MIRA proposal is focused on developing and implementing
methods to uncover functional roles of RNA glycosylation and we will approach the complex biology of
glycoRNAs in a systematic fashion. Initially we will develop novel chemical approaches to label glycans in the
context of RNA. My proposed strategy of selective carboxylic acid labeling represents an innovative new
approach to detecting glycoRNA, without the need for synthetic metabolic reporters. These tools will be easily
implemented across cell types and species enabling others in the scientific community. We will apply these tools
and other molecular assays to expand our understanding of the composition of the cell surface in the context of
glycoRNA. Biochemical, biophysical, and imaging-based strategies will be used to define the molecular
neighborhoods of glycoRNAs as well as the chemical nature of the RNA-glycan linkage; all together providing a
more complete picture of the mammalian cell surface. Finally, we will develop the first evidence of glycoRNAs in
non-mammalian organisms. First focusing on two major strains of yeast (S. cerevisiae and S. pombe) with robust
culturing, functional, and genetic tools that will allow for rapid dissection of the biogenesis pathway for eventual
engineering purposes. Expanding to other organisms including prokaryotes (pathogenic and not) as well as other
multicellular eukaryotes like C. elegans will better define the scope of glycoRNA biosynthesis and more robustly
equip us to generate synthetic glycoRNAs. More broadly, we intend to advance the general model of how cells
in...

## Key facts

- **NIH application ID:** 10883771
- **Project number:** 5R35GM151157-02
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Ryan Alexander Flynn
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $442,500
- **Award type:** 5
- **Project period:** 2023-07-14 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10883771

## Citation

> US National Institutes of Health, RePORTER application 10883771, Mechanisms and functions of cell surface glycoRNAs (5R35GM151157-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10883771. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*