Novel Truncated Peptide Derived From circCDYL Exacerbates Cardiac Hypertrophy

Area of Science:

• Cardiovascular Biology
• Molecular Biology
• Epigenetics

Background:

• Circular RNAs (circRNAs) are increasingly recognized for their roles in heart disease.
• Many cardiac circRNAs remain functionally uncharacterized, necessitating further investigation.
• This study focuses on identifying novel circRNAs involved in pathological cardiac hypertrophy.

Purpose of the Study:

• To explore potential cardiac circRNA candidates involved in pathological cardiac hypertrophy.
• To elucidate the functional role and mechanism of identified circRNAs in cardiac hypertrophy.

Main Methods:

• Utilized RNA-sequencing data to identify cardiac hypertrophy-related circRNAs.
• Induced cardiomyocyte hypertrophy in vitro using Ang II and in vivo in mice.
• Performed gain-of-function and loss-of-function assays to assess RNA and protein effects.

Main Results:

• Identified circCDYL, significantly induced by Ang II in cardiomyocytes, promoting hypertrophy.
• CircCDYL encodes a truncated CDYL peptide (tCDYL-100) via N6-methylation, driving hypertrophy.
• tCDYL-100 disrupts the REST-CDYL-EHMT2 complex, activating rhoa and nppb transcription.

Conclusions:

• Uncovered a novel circRNA-derived peptide, tCDYL-100, in pathological cardiac hypertrophy.
• Revealed a regulatory mechanism involving N6-methyladenosine-circRNA-histone methylation.
• Demonstrated circCDYL's role in promoting cardiac hypertrophy through epigenetic modulation.