A long noncoding RNA CHAIR protects the heart from pathological stress

Area of Science:

• Genomics
• Molecular Biology
• Cardiovascular Research

Background:

• Mammalian genomes are extensively transcribed, yielding numerous long noncoding RNAs (lncRNAs).
• The specific functions of lncRNAs, particularly in the context of heart disease, are not fully understood.
• Tissue-specific lncRNAs are hypothesized to play a role in heart failure progression.

Purpose of the Study:

• To investigate the role of cardiac-enriched lncRNAs in heart failure.
• To identify and characterize a novel lncRNA involved in cardiac function and disease.

Main Methods:

• Identification and characterization of cardiac-enriched lncRNAs.
• Analysis of lncRNA expression in developing, adult, and failing hearts (mice and humans).
• Functional studies involving lncRNA knockout and restoration in stress-induced heart failure models.
• Investigation of epigenetic mechanisms involving DNMT3A and lncRNA CHAIR interactions.

Main Results:

• A cardiac-enriched lncRNA, cardiomyocyte hypertrophic associated inhibitory RNA (CHAIR), was identified.
• CHAIR expression is low in embryonic hearts and high in adult hearts, decreasing during cardiac hypertrophy and failure.
• Loss of CHAIR accelerates heart failure progression and exacerbates hypertrophy, while its restoration rescues cardiac function.
• DNMT3A represses CHAIR expression, and CHAIR inhibits DNMT3A activity, revealing a feedback loop.

Conclusions:

• CHAIR is a novel cardioprotective lncRNA that represses heart failure.
• CHAIR functions through an epigenetic mechanism involving DNMT3A.
• Targeting CHAIR may offer a therapeutic strategy for heart failure.