# Chemical Biology Approaches for Investigating RNA-Protein Interactions

> **NIH NIH R35** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $542,079

## Abstract

Recent studies have shown that RNAs are invariably bound to and often modified by RNA-binding proteins
(RBPs). Thus, it is no surprise that RBPs have been found to play key roles in regulating many aspects of coding
and non-coding RNA biology, including RNA processing, nuclear export, cellular transport, function, localization,
and stability. These efforts are carried out by >1,500 unique RBPs that utilize a variety of RNA-binding domains
to achieve oftentimes specific and high affinity interactions with target transcripts; however, non-canonical RBPs
have also been identified. Disruption of this complex network of RNA-protein interactions (RPIs) has been
implicated in a number of human diseases. Thus, the targeting of RBPs and RPIs has arisen as a new frontier
in RNA-targeted drug discovery. Recent work from our laboratory has resulted in the development of tools and
technologies applicable to the study of RPIs, including biochemical and cellular assays for the detection,
validation, and screening of RPIs; the discovery of small molecule, peptide, and natural product inhibitors of RPIs
and RBPs; and the discovery of new biological insights into the regulation of RPIs and RBPs. Building upon our
recent progress, the research proposed in this project is focused on three major research directions. For the first
project, we will continue our efforts to develop our laboratory’s live-cell RPI assay technology, RNA interaction
with Protein-mediated Complementation Assay (RiPCA), as a scalable and robust platform for validating and
manipulating cellular RPIs. For the second project, we will utilize RiPCA to expand our access to high-quality
chemical probes for targeting cellular RPIs. For the third project, we will use mechanistically distinct chemical
probes targeting eIF4E to explore the context-dependence of RBP regulation and activity. Through these
combined research efforts, we will enable the study of RBPs and RPIs in living cells to promote our understanding
of this new frontier of cellular biology with great potential for the development of new medicines.

## Key facts

- **NIH application ID:** 10840169
- **Project number:** 1R35GM153185-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Amanda Garner
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $542,079
- **Award type:** 1
- **Project period:** 2024-09-01 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10840169

## Citation

> US National Institutes of Health, RePORTER application 10840169, Chemical Biology Approaches for Investigating RNA-Protein Interactions (1R35GM153185-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10840169. Licensed CC0.

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