# Investigating the role of long non-coding RNAs in regulation of DNA methylation

> **NIH NIH K00** · UNIVERSITY OF COLORADO · 2022 · $54,117

## Abstract

Project Summary
Aberrant DNA methylation patterns are early hallmarks of cancer. In healthy cells, there are “writers” that
establish these methylation marks and “erasers” that remove them in specific cell types and at varying points
during cell differentiation. Proper regulation of DNA methylation is critical for normal cell function. An important
class of writers is the DNA methyl transferases (DNMTs). DNMTs are responsible both for establishing DNA
methylation patterns as well as maintaining them during successive rounds of DNA replication. DNMTs are often
mutated in cancers and the precise mechanisms for how DNMTs promote gene-specific DNA methylation in
healthy cells are not well understood. Recent evidence has suggested that RNA plays important roles in
regulating epigenetic marks. For example, several lncRNAs have been shown to interacts with DNMTs, primarily
with the maintenance methylase DNMT1. In this extension proposal I aim to investigate the regulation of DNMT1
by RNAs. I will initially aim to elucidate the molecular basis for how RNA interacts with DNMT1 by uncovering
core structural features required for DNMT1 binding. I will follow up on the preliminary data I have gathered
during my K00 funding which includes uncovering a high affinity of DNMT1 for GU-rich RNA. Additionally, I have
found that DNMT1 binds with high affinity to its own mRNA, specifically it’s 3’ UTR, which interestingly is also
very GU-rich. I will determine the nature of this specific interaction by performing Cryo-EM on a DNMT1/GU-rich
RNA complex together with additional biochemical assays to better understand the binding preference of DNMT1
for various RNAs. Together, this proposal will help elucidate how DNA methylation is misregulated in cancer and
will additionally provide information about how RNAs help regulate this important process. Gaining an
understanding of the molecular basis for how RNAs interact with DNMT1 may provide structural targets for use
in the development of tissue-specific cancer therapeutics.

## Key facts

- **NIH application ID:** 10623599
- **Project number:** 3K00CA212439-06S1
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** Linnea Jansson-Fritzberg
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $54,117
- **Award type:** 3
- **Project period:** 2022-09-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10623599

## Citation

> US National Institutes of Health, RePORTER application 10623599, Investigating the role of long non-coding RNAs in regulation of DNA methylation (3K00CA212439-06S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10623599. Licensed CC0.

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