Tiny RNA switches that control heart gene activity
uORF-mediated Translational Control of Cardiac Transcription Factor Expression
This project develops RNA-based molecules to change how heart cells make key proteins, aiming to prevent or reduce harmful heart muscle enlargement.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Rochester NIH-funded |
| Lab location | 1 site (Rochester, United States) |
| Project ID | NIH-11314572 on NIH RePORTER |
What this research studies
Researchers found small coding regions called uORFs in the messages that make heart proteins and think these can lower production of important heart genes like GATA4. They use computer analysis, biochemical tests, and human stem-cell models edited with CRISPR to see how uORFs affect heart cell size and function. A mouse model with a changed uORF that causes spontaneous heart enlargement will be studied under normal and stress conditions. The team has designed two types of antisense oligonucleotides (ASOs) to alter the RNA structure and restore normal protein production, and they will test these in cells and mice to measure effects on heart cells and tissue.
Who could benefit from this research
Good fit: People with heart muscle enlargement (cardiac hypertrophy) or certain genetic cardiomyopathies linked to abnormal gene regulation would be the most relevant candidates.
Not a fit: Patients whose heart problems are caused mainly by blocked coronary arteries, severe valve disease, infection, or other non-translational causes are unlikely to benefit from this specific approach.
Why it matters
Potential benefit: If successful, this work could lead to new RNA-based therapies that restore proper heart protein levels and prevent or reverse cardiac hypertrophy.
How similar studies have performed: Antisense oligonucleotide drugs have helped patients with other genetic diseases, but targeting uORFs in heart genes is a novel strategy with limited prior human data.
Where this research is happening
Rochester, United States
- University of Rochester — Rochester, United States (Active)
Researchers
- Principal investigator: Yao, Peng — University of Rochester
- Study coordinator: Yao, Peng
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.