# An RNA editing platform to investigate the dynamic RNA interactome

> **NIH NIH R01** · PRINCETON UNIVERSITY · 2024 · $328,000

## Abstract

PROJECT SUMMARY/ABSTRACT
A major mechanism of post-transcriptional gene expression regulation occurs through the binding of RNA
transcripts with RNA-binding proteins (RBPs), a large class of cellular proteins consisting of over 1500 members.
Identifying the native substrates of RBPs and characterizing the function of these interactions remains a
significant challenge in biology. Further, oligonucleotides and small molecules that target RNA-protein
interactions and modulate protein expression have been recently deployed in the clinic and promise to provide
a new therapeutic modality for the treatment of human diseases.
We have developed TRIBE-ID, an RNA editing approach to interrogate dynamic RNA-protein interactions in a
small molecule-dependent manner. We applied our approach to profile the RNA substrates of the RBP G3BP1,
a central component of stress granule condensates. Here, we propose to further develop and apply TRIBE-ID
as a general platform to investigate RNA-binding events in cells. We will advance the efficiency and generality
of RNA editing for interactomic studies and investigate the trafficking and post-transcriptional regulation of RNA
stability/translation by cytoplasmic biomolecular condensates. Further, we will develop RNA editing approaches
to investigate small-molecule RNA interactions. Our project has the following specific aims:
Aim 1. Develop an RNA editing platform with improved generality, efficiency, and molecular resolution.
Aim 2: Characterize regulation of RNA stability/translation by biomolecular condensate-forming RBPs.
Aim 3: Develop an RNA editing approach to investigate RNA-binding small molecule therapeutics.
Our findings will provide new approaches for studying dynamic RNA-protein interactions and RNA-binding small
molecules and reveal new insights into the formation and function of phase-separated biomolecular
condensates. These studies should advance our understanding of fundamental RNA regulatory mechanisms
and accelerate the development and characterization of RNA-targeted therapeutics.

## Key facts

- **NIH application ID:** 10981065
- **Project number:** 1R01GM152748-01A1
- **Recipient organization:** PRINCETON UNIVERSITY
- **Principal Investigator:** Ralph Elliot Kleiner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $328,000
- **Award type:** 1
- **Project period:** 2024-09-21 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10981065

## Citation

> US National Institutes of Health, RePORTER application 10981065, An RNA editing platform to investigate the dynamic RNA interactome (1R01GM152748-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10981065. Licensed CC0.

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