# tRNA-derived non-coding RNAs in ASM function and in asthma

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 2021 · $588,083

## Abstract

Project Summary and Abstract: The goal of our proposed studies is to elucidate the expression profiles and
molecular functions of short non-coding RNAs (ncRNAs) in the pathogenesis of asthma. Asthma is a chronic
inflammatory disease characterized by inflammation, mucus production, airway re-modeling, and hyper-
responsiveness. In asthma, allergic inflammatory mediators, such as cytokines, act on resident airway cells
[airway smooth muscle (ASM) cells, epithelial (AE) cells and fibroblasts (LF)] causing their structural and
functional changes. However, knowledge gaps remain in our understanding of the mechanisms by which
inflammatory mediators modulate cellular phenotypes. Although transcriptional regulation of gene expression in
resident airway cells has been extensively studied, regulatory mechanisms at post-transcriptional steps remain
elusive. In this context, short ncRNAs have evolved as one of the key post-transcriptional regulators of gene
expression. Previous transcriptome profiling for short ncRNA analyses relied mainly on standard RNA-seq
methods which fail to detect many RNA species. Cyclic phosphate-containing RNAs (cP-RNAs), that harbor a
cyclic phosphate (cP) at their 3′-end, are one such RNA species not captured by RNA-seq, because cP prevents
3′-adapter ligation. Their absence in RNA-seq data makes cP-RNAs an invisible, hidden component of
transcriptomes. Importantly, cP-RNAs are expressed as functional molecules. For example, angiogenin-
generated 5′-tRNA halves, containing a cP and thus belonging to cP-RNAs, have functional significance in stress
response, translational regulation, and cell proliferation, and are associated with neurodegenerative diseases
and cancers. We propose that 5′-tRNA halves and other cP-RNAs play important roles in asthma pathobiology.
In preliminary studies, we found that mouse lung expresses specific 5′-tRNA halves and cP-RNAs whose levels
are upregulated during allergic inflammation caused by inhaled challenge of house dust mite (HDM).
Furthermore, in human ASM cells, 5′-tRNA halves function to regulate cellular focal adhesion, migration, and
proliferation. These results allowed us to hypothesize that inflammatory mediators upregulate the levels of 5′-
tRNA halves/cP-RNAs, which contributes to airway cellular phonotypic changes in the molecular pathogenesis
of asthma. By using our developed cP-RNA-seq, we propose to fully elucidate the regulation of the expression
of 5′-tRNA halves/cP-RNAs mediated by asthmatic conditions in human lung and plasma samples and in human
ASM cells, AE cells, and LFs (Aim 1). We further propose to assess the functional effects of 5′-tRNA halves/cP-
RNAs on cellular focal adhesion, migration, proliferation, and morphology of ASM cells (Aim 2) and to investigate
the molecular mechanisms underlying the functional effects of those RNAs (Aim 3). The proposed studies will
reveal a novel ncRNA-engaged pathway in asthma pathogenesis and will support the exploration of biomarkers
in...

## Key facts

- **NIH application ID:** 10168602
- **Project number:** 5R01HL150560-02
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **Principal Investigator:** Deepak A Deshpande
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $588,083
- **Award type:** 5
- **Project period:** 2020-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10168602

## Citation

> US National Institutes of Health, RePORTER application 10168602, tRNA-derived non-coding RNAs in ASM function and in asthma (5R01HL150560-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10168602. Licensed CC0.

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