# Deciphering the role of a circadian lncRNA in cardiac remodeling

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2022 · $716,778

## Abstract

Project Summary
 Heart failure (HF) is associated with a 5-year mortality of 50% and the incidence is still rising with most
cases associated with ischemic cardiomyopathy. Identifying novel strategies to counteract cardiac pathological
remodeling post myocardial infarction (MI) is of urgent clinical need. Long non-coding RNAs (lncRNA) have
recently emerged as regulators of cardiac development and disease. However, the function of most lncRNAs
remains unknown.
 We have characterized the first cardiac specific circadian lncRNA Circa, which affects cardiac remodeling
post MI through regulating alternative splicing. To better understand the molecular mechanisms of Circa and its
partner proteins in the heart, we propose the following specific aims: 1. Identify the RNA structures that are
required for Circa nuclear localization and interaction with spliceosome. We will use the state-of-the-art chemical
probing technique to define the secondary structure of Circa, then use structure mutants to identify its functional
motifs. 2. Determine whether Circa acts in trans and whether its function is dependent on its oscillatory
expression. We will unambiguously determine Circa function as a transcript by a series of “rescue” experiments
in the novel knock out mice we created. Time restricted expression will be used to test the necessity of the
oscillatory expression. 3. Define the molecular basis by which Circa affects splicing in the heart. Our preliminary
data suggests Circa may suppress splicing regulator hnRNPA1. We will test the functional interaction between
Circa and hnRNPA1 using a cardiac target gene we identified. We will further investigate the role of hnRNAPA1
in the post MI remodeling by identifying its splicing targets using eCLIPseq/RNAseq and test the function of
hnRNPA1 in vitro and in vivo. Completion of this proposal will have significant impact in understanding splicing
regulation in the heart during post MI pathological remodeling and potentially expand our therapeutic strategies
for HF treatment.

## Key facts

- **NIH application ID:** 10442269
- **Project number:** 1R01HL150589-01A1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Lilei Zhang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $716,778
- **Award type:** 1
- **Project period:** 2022-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10442269

## Citation

> US National Institutes of Health, RePORTER application 10442269, Deciphering the role of a circadian lncRNA in cardiac remodeling (1R01HL150589-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10442269. Licensed CC0.

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