# Non-coding RNA structure change in Chronic Obstructive Pulmonary Disease

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $696,520

## Abstract

SUMMARY
Chronic obstructive pulmonary disease (COPD) is a complex genetic disease associated with over 160 genes
coupled with numerous environmental factors. In most cases, the single-nucleotide polymorphisms (SNPs) most
strongly associated with COPD do not alter the protein coding sequence of genes but instead map to non-coding,
but often transcribed, regions of the genome, including UTRs and introns. Our collaborative work to date has
focused on how 5' and 3' UTR RNA structures are affected by SNPs and has revealed that many sequence
changes modulate RNA structures and alter translation of COPD-associated genes. Understanding of the
interrelationships between RNA structure and gene expression is in its infancy, has primarily focused on the
based-paired secondary structure of exons, and has been severely limited by our inability to fully explore RNA
structure in cells. We have developed three novel chemistry-based RNA structure probing strategies that allow
us to (i) investigate precursor mRNA structure in cells, (ii) identify regions in UTRs that likely adopt true higher-
order tertiary structure, and (iii) determine through-space contacts in RNAs and develop three-dimensional
models of their complex structures. These technologies open broad and long-term research areas into how
complex RNA structures modulate gene expression and how RNA structure is changed by SNPs associated with
disease. Another critical, allied development has been collection of extensive population-wide transcriptomic
(RNA-seq) data of COPD patient lung and blood tissues through consortia in which we participate. Based on
these transcriptomic data and their analysis, we have characterized important changes in both splicing and
polyadenylation of COPD associated genes; both processing events have important consequences on gene
expression. Our program also leverages substantial exploratory work that shows that RNA structure in coding
sequences of genes associated with COPD modulates their translation. For this proposal, we are now in a unique
position to leverage novel technologies and transcriptomic analyses to interrogate how RNA structure regulates
mRNA translation of COPD-associated genes. We expect to identify RNA structures that comprise robust targets
for RNA therapeutics designed to alter post-transcriptional gene regulation of protein expression. This project
will ultimately reveal new principles for how RNA structure regulates protein translation and alternative splicing
and will identify RNA regulatory structures in the human transcriptome associated with COPD.

## Key facts

- **NIH application ID:** 10912010
- **Project number:** 5R01HL111527-11
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Alain T Laederach
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $696,520
- **Award type:** 5
- **Project period:** 2012-01-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10912010

## Citation

> US National Institutes of Health, RePORTER application 10912010, Non-coding RNA structure change in Chronic Obstructive Pulmonary Disease (5R01HL111527-11). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10912010. Licensed CC0.

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