Endogenous RBM4 prevents Ang II-induced cardiomyocyte hypertrophy via downregulating the expression of PTBP1

Area of Science:

• Cardiovascular Biology
• Molecular Mechanisms of Disease
• Gene Regulation

Background:

• Pathological cardiac hypertrophy involves aberrant cardiomyocyte gene expression.
• The precise molecular regulators driving cardiac hypertrophy remain incompletely understood.
• Identifying novel therapeutic targets is crucial for managing cardiac hypertrophy.

Purpose of the Study:

• To investigate the role of RNA-binding motif protein 4 (RBM4) in regulating cardiomyocyte hypertrophy.
• To elucidate the molecular mechanisms by which RBM4 influences cardiac hypertrophy.
• To identify upstream regulators of RBM4 in the context of cardiac hypertrophy.

Main Methods:

• In vitro studies using cardiomyocyte cell models.
• Manipulation of RBM4 expression (knockdown and overexpression).
• Analysis of protein and mRNA levels, including m6A methylation and translation efficiency.

Main Results:

• RBM4 acts as an endogenous protector against cardiomyocyte hypertrophy.
• RBM4 protein levels increase under angiotensin II (Ang II) stimulation.
• RBM4 represses hypertrophy by down-regulating polypyrimidine tract-binding protein 1 (PTBP1) expression.
• Ang II-induced m6A methylation of RBM4 mRNA enhances its translation via YTHDF1.

Conclusions:

• RBM4 plays a protective role in mitigating cardiac hypertrophy.
• A novel pathway involving m6A, RBM4, and PTBP1 is identified in cardiac hypertrophy.
• RBM4 represents a potential therapeutic target for pathological cardiac hypertrophy.