MBNL1 regulates programmed postnatal switching between regenerative and differentiated cardiac states

Area of Science:

• Cardiology
• Developmental Biology
• Molecular Biology

Background:

• Understanding cardiomyocyte maturity is crucial for cardiac development and regeneration.
• Identifying regulators of differentiated states is key for therapeutic strategies.

Approach:

• Investigated the role of RNA binding protein Muscleblind-like 1 (MBNL1) in cardiomyocyte differentiation and regeneration.
• Analyzed transcriptome-wide RNA stability control by MBNL1.
• Examined MBNL1's impact on cell cycle regulators and estrogen-related receptor signaling.

Key Points:

• MBNL1 overexpression led to premature cardiomyocyte maturation, dysfunction, and hypoplasia.
• MBNL1 loss promoted cardiomyocyte cell cycle entry and proliferation by altering cell cycle inhibitor stability.
• MBNL1 stabilized the estrogen-related receptor signaling axis, essential for cardiomyocyte maturity.
• Modulating MBNL1 dose controlled the window for cardiac regeneration, affecting myocyte proliferation.

Conclusions:

• MBNL1 acts as a critical regulator of cardiomyocyte differentiated states.
• MBNL1 functions as a transcriptome-wide switch between regenerative and mature myocyte states.
• MBNL1 modulation offers a potential therapeutic strategy for cardiac regeneration.