# Elucidating the Structure and the Function of Non-Coding RNA-LSD1 Interactions

> **NIH NIH R01** · MARQUETTE UNIVERSITY · 2021 · $8,516

## Abstract

Abstract
This research project is centered on the hypothesis that ribonucleic acid (RNA) structure and
RNA-chromatin associated protein interactions play crucial roles in maintaining genome
stability. Non-coding RNAs (ncRNAs) serve as key regulators of gene expression and are
known to physically associate with chromatin-associated proteins to organize changes in gene
architecture during specific development stages of the cell. A subset of these RNA-protein
interactions are linked to ageing, cancer metastasis, and neuronal development. As genomic
approaches begin to identify RNA-protein associations and their links to cancer, there remains
limited information about epigenetic-based RNA binding proteins at the molecular level. We
seek to understand how RNA functionally interacts with the lysine specific demethylase-1
(LSD1) protein enzyme. LSD1 is an essential histone methylation regulator and has oncogenic
properties in several cancers including: prostate, bladder, neuroblastoma, lung, and breast
cancer. LSD1 is implicated in cancer through its vast interaction network. LSD1 also interacts
with many RNA molecules involved in cell differentiation and can function to regulate conserved
RNA-mediated repressor complexes in the cell. An ncRNA, termed TERRA, enables LSD1 to
interact with a DNA double strand break repair enzyme at the ends of chromosomes
(telomeres), demonstrating that the RNA binding properties of LSD1 are important for gene
regulation. TERRA is a regulatory RNA that is transcribed from yeast to humans and can adopt
a non-canonical guanine quadruplex (GQ) RNA architecture in vitro and in vivo. TERRA’s
abundance in the cell correlates with progressive telomere shortening and the stabilization of
telomeric heterochromatin. We hypothesize that RNA-LSD1 assemblies play key roles in gene
expression and propose that GQ RNAs serve as crucial regulators of chromatin-associated
proteins. The proposed studies will 1) elucidate the biochemical and structural mechanisms of a
TERRA RNA-LSD1 interaction and 2) examine how non-canonical structured RNAs contact
LSD1 to influence telomeric regulatory pathways. The long-term goal of this project is to
understand how RNA structure influences LSD1 regulatory networks. Results from these
studies will provide insight into the mechanisms of RNA-based epigenetic regulation and serves
as a starting point in the development of ‘tailored’ probes that target histone methylation
regulators in a pathway-specific manner.

## Key facts

- **NIH application ID:** 10393402
- **Project number:** 3R01GM120572-06S1
- **Recipient organization:** MARQUETTE UNIVERSITY
- **Principal Investigator:** Nicholas J Reiter
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $8,516
- **Award type:** 3
- **Project period:** 2021-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10393402

## Citation

> US National Institutes of Health, RePORTER application 10393402, Elucidating the Structure and the Function of Non-Coding RNA-LSD1 Interactions (3R01GM120572-06S1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10393402. Licensed CC0.

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