# Functional characterization of cell surface RNA biology

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2024 · $864,515

## Abstract

PROJECT SUMMARY / ABSTRACT
The composition and organization of the cell surface are critically important for cell-to-cell communication and
for the ability of cells to interact with their surrounding environment. The cell surface is decorated with myriad
glycosylated transmembrane proteins for which there is a molecular understanding of their function and cell
surface presentation. Surprisingly, RNA and RNA-binding proteins (RBPs) are also glycosylated and
components of the cell surface. However, is unknown what glycosylated RNAs and RBPs do at the cell surface.
This unexplored area of biology represents a major knowledge gap in our understanding of both the RNA and
cell surface fields. Thus, the immediate goal of this proposal is to close this knowledge gap and to create the
conceptual and technical foundations that will enhance our understanding and exploration, respectively, of the
biology of RNA at the surface of the cell. To achieve this, we propose to explore three fundamental, but
outstanding, hypotheses. Importantly, these hypotheses are established on sound logic of the known biology of
RNA and RBPs and supported by the published literature and preliminary data. Hypothesis 1 explores the
molecular, biochemical, and biophysical activities of the cell surface localized RBPs DDX21 and NCL in the
extracellular space. Hypothesis 2 takes an unbiased genetic approach to determine how cell surface RBPs are
trafficked to the cell surface, given that they lack a classical membrane-targeting signal. Hypothesis 3 explores
the intersection between cell surface RBPs and RNA in disease pathogenesis by focusing on the functional
characterization of cell surface RBPs that possess cell-penetrating activities. The expected outcomes of this
research are to reveal that the biochemical activities of RBPs are not restricted to the intracellular space of the
cell, but also to the cell surface. The significance of the proposed research lies in expanding the field of RNA to
the surface of cells and providing proof of concept of the importance of cell surface RBPs in human disease.
While high-risk, the proposed research addresses an important problem and has the potential to be
transformative. Hence its suitability for the Transformative Research Award.

## Key facts

- **NIH application ID:** 10917771
- **Project number:** 1R01ES037423-01
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Ryan Alexander Flynn
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $864,515
- **Award type:** 1
- **Project period:** 2024-09-03 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10917771

## Citation

> US National Institutes of Health, RePORTER application 10917771, Functional characterization of cell surface RNA biology (1R01ES037423-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10917771. Licensed CC0.

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