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

> **NIH NIH R01** · MARQUETTE UNIVERSITY · 2021 · $296,338

## 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:** 10113636
- **Project number:** 5R01GM120572-06
- **Recipient organization:** MARQUETTE UNIVERSITY
- **Principal Investigator:** Nicholas J Reiter
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $296,338
- **Award type:** 5
- **Project period:** 2017-08-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10113636

## Citation

> US National Institutes of Health, RePORTER application 10113636, Elucidating the Structure and the Function of Non-Coding RNA-LSD1 Interactions (5R01GM120572-06). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10113636. Licensed CC0.

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