RBM15 Protects From Myocardial Infarction by Stabilizing NAE1

Area of Science:

• Molecular Biology
• Cardiovascular Research
• Epigenetics

Background:

• RNA-binding proteins regulate diverse biological processes.
• The role of RBM15, an RNA methylation regulator, in cardiovascular disease is largely unknown.
• Myocardial infarction (MI) is a critical cardiovascular condition with complex molecular underpinnings.

Purpose of the Study:

• To investigate the function and mechanism of RBM15 in myocardial infarction (MI).
• To explore the role of N6-methyladenosine (m⁶A) RNA methylation in MI.
• To identify RBM15 targets and their impact on cardiomyocyte function.

Main Methods:

• Methylated RNA immunoprecipitation sequencing (MeRIP-seq) to analyze m⁶A profiles in MI and normal tissues.
• Assessment of RBM15 overexpression effects on cardiomyocyte apoptosis and cardiac function in a mouse MI model.
• Investigation of RBM15 targets, specifically the NEDD8 activating enzyme E1 subunit, using inhibitors like MLN4924.

Main Results:

• m⁶A levels were elevated in MI tissues compared to normal tissues.
• RBM15 overexpression attenuated cardiomyocyte apoptosis and improved cardiac function post-MI.
• RBM15 overexpression increased the expression and stability of the NEDD8 activating enzyme E1 subunit via enhanced m⁶A methylation.

Conclusions:

• Elevated m⁶A methylation, regulated by RBM15, acts as a protective mechanism in MI.
• RBM15 is upregulated in MI and promotes cardiac function by stabilizing target genes involved in apoptosis.
• RBM15-mediated m⁶A regulation presents a potential therapeutic target for MI.