RNA Processing in Cardiac Hypertrophy: Coordinating Physiological Adaptation and Pathological Remodeling.

Area of Science:

• Cardiovascular Biology
• Molecular Biology
• Epigenetics

Background:

• Cardiac hypertrophy involves complex gene expression changes.
• Post-transcriptional RNA processing is a key factor in cardiac homeostasis.
• Understanding RNA modifications, splicing, stability, and editing is crucial.

Purpose of the Study:

• To review RNA processing in physiological and pathological cardiac hypertrophy.
• To highlight epitranscriptomic marks (m6A, m5C, m7G) and RNA-binding proteins.
• To explore the role of RNA processing in adaptive and maladaptive cardiac remodeling.

Main Methods:

• Literature review of RNA modifications, alternative splicing, mRNA stability, and RNA editing.
• Analysis of key RNA-binding proteins and adenosine deaminases acting on RNA (ADAR1/2).
• Examination of specific examples like RBFOX2, RBM20, and METTL14 in exercise-induced hypertrophy.

Main Results:

• Exercise-induced hypertrophy involves adaptive RNA processing supporting sarcomere organization, calcium handling, and survival.
• Pathological hypertrophy features dysregulated RNA programs promoting maladaptive remodeling and heart failure.
• Specific regulators (METTL3, YTHDF2, RBM24, ADAR2) balance adaptive and maladaptive responses.

Conclusions:

• RNA processing plays a dual role in cardiac hypertrophy, contributing to both adaptation and maladaptation.
• Targeting RNA processing nodes (e.g., METTL3, RBM24) offers potential therapeutic strategies.
• RNA-targeted interventions represent a promising avenue for precision cardiovascular therapy.