Abstract
Small RNAs, especially the microRNAs, have been revealed to play great roles in heart development and congenital heart defects. Several studies have shown dysregulated miRNAs in ventricular tissues of Tetralogy of Fallot (TOF) patients. In the present study, we conducted high throughput sequencing to obtain the global profiling of small RNA transcriptome in heart right ventricular samples from 10 age -matched TOF patients. These samples showed dominant composition of miRNA and mitochondrial associated RNAs. By sRNA cluster identification and differential gene expression analysis, significant sexual difference was discovered for sRNA expression in TOF patients. miR-1/miR-133, which have been identified as essential for cardiac development, account for the most variance of sRNA expression between sexes in TOF hearts.
Highlights
During the normal process of heart development and growth, a genetic network involving precise temporal and spatial gene regulation is required
We found that Tetralogy of Fallot (TOF) heart sRNA transcriptome have over represented composition of miRNAs and mitochondrion associated sRNAs, a significant difference of sRNA expression was shown between male and female samples
A substantial proportion of sRNA originated from mitochondrion sRNAs, which might be a unique feature for heart tissues since cardiomyocytes enormous mitochondrion
Summary
During the normal process of heart development and growth, a genetic network involving precise temporal and spatial gene regulation is required. Small non-coding RNAs (sRNAs) have been shown to play important parts in cardiac gene expression network. MiR-1 transgenic mics display similar phenotype as Hand[2] mutant mice[2,3]; The miRNA-17–92 cluster have been suggested function in promoting cardiac progenitor differentiation in a dose-dependent manner; disruption of miR-138 by morpholino and antagomir in zebrafish could result in expression of atrioventricular canal specific genes in ventricular chamber, lead to abnormal cardiac patterning. Several evidence from microarray analysis have shown that miRNAs should be dysregulated in TOF heart tissues[5,6,7,8]. We found that TOF heart sRNA transcriptome have over represented composition of miRNAs and mitochondrion associated sRNAs, a significant difference of sRNA expression was shown between male and female samples
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