Whole genome expression differences in human left and right atria ascertained by RNA sequencing

Area of Science:

• Cardiovascular Molecular Biology
• Cardiac Electrophysiology
• Genomics and Transcriptomics

Background:

• The left and right atria display varying susceptibility to arrhythmias.
• Left atrial arrhythmias are observed more frequently than right atrial arrhythmias.
• The molecular underpinnings of these differential susceptibilities remain largely unexplored.

Purpose of the Study:

• To investigate the molecular basis for differential arrhythmia susceptibility between the left and right atria.
• To compare micro (mi)RNA and messenger RNA (mRNA) expression profiles in human left and right atria.

Main Methods:

• Whole-genome expression analysis using next-generation sequencing of small RNAs (including miRNAs) and poly-A-enriched mRNAs.
• Analysis of four paired human left-right atrial samples.
• Identification of differentially expressed miRNAs and mRNAs using paired sample statistical analysis.

Main Results:

• Significant differences in the expression of 32 miRNAs were identified between the left and right atria (p < 0.01).
• Hsa-miR-143 was the most highly expressed miRNA.
• A substantial number of differentially expressed mRNAs were found: 746 (FDR < 0.001) and 2292 (FDR < 0.05).
• Enrichment analysis revealed specific transcription factor binding motifs and miRNA target sequences in differentially expressed genes.
• Eleven novel noncoding RNAs with unknown functions were also differentially expressed.

Conclusions:

• Significant disparities exist in miRNA and mRNA expression profiles between the left and right atria.
• These molecular differences provide potential insights into the increased arrhythmogenesis observed in the left atrium.
• Further research into these differentially expressed molecules could reveal novel therapeutic targets for atrial arrhythmias.