# Protein Disorder as a Mechanism of RNA Binding and Regulation

> **NIH NIH R35** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $388,750

## Abstract

Project Abstract
As factors involved in all aspects of RNA processing, RNA binding proteins (RPBs) are master regulators of
gene expression. Despite this critical role, gaps remain in our understanding of how RBPs interact with RNA.
Generally, RBPs have been considered to interact with typically single-stranded RNA via folded RNA-binding
domains. However, many RBPs also have inherently disordered domains of low compositional complexity (low
complexity domains, LCDs). In our current understanding of how RBPs interact with RNA, LCDs mediate protein-
protein interactions and/or weak, non-specific RNA interactions. In contrast, a growing body of literature, and our
own data, indicate LCDs are capable of specific binding to highly stable guanine-based helical RNA structures.
These findings represent a reversal of the canonical binding mode: rather than folded protein binding to
unstructured RNA, we have observed folded RNA binding to unstructured protein. My research program asks i)
how do RBP LCDs interact with RNA? And, ii) what are the functional consequences of LCD-RNA interactions?
This proposal outlines my research program to decipher basic mechanisms and dynamics of RBP-RNA
interactions and define their role in normal and pathogenic pathways combining unbiased biochemical
approaches with cell-based genomic strategies. Data generated from the proposed research will contribute
broadly across all areas of cell biology by illuminating a more complete picture of RBP-RNA interactions.

## Key facts

- **NIH application ID:** 10275803
- **Project number:** 1R35GM142864-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Daniel Issac Dominguez
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $388,750
- **Award type:** 1
- **Project period:** 2021-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10275803

## Citation

> US National Institutes of Health, RePORTER application 10275803, Protein Disorder as a Mechanism of RNA Binding and Regulation (1R35GM142864-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10275803. Licensed CC0.

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