Abstract
Adenosine-to-inosine (A-to-I) RNA editing meditated by adenosine deaminases acting on RNA (ADARs) enzymes is a widespread post-transcriptional event in mammals. However, A-to-I editing in skeletal muscle remains poorly understood. By integrating strand-specific RNA-seq, whole genome bisulphite sequencing, and genome sequencing data, we comprehensively profiled the A-to-I editome in developing skeletal muscles across 27 prenatal and postnatal stages in pig, an important farm animal and biomedical model. We detected 198,892 A-to-I editing sites and found that they occurred more frequently at prenatal stages and showed low conservation among pig, human, and mouse. Both the editing level and frequency decreased during development and were positively correlated with ADAR enzymes expression. The hyper-edited genes were functionally related to the cell cycle and cell division. A co-editing module associated with myogenesis was identified. The developmentally differential editing sites were functionally enriched in genes associated with muscle development, their editing levels were highly correlated with expression of their host mRNAs, and they potentially influenced the gain/loss of miRNA binding sites. Finally, we developed a database to visualize the Sus scrofa RNA editome. Our study presents the first profile of the dynamic A-to-I editome in developing animal skeletal muscle and provides evidences that RNA editing is a vital regulator of myogenesis.
Highlights
RNA editing represents a widespread post-transcriptional modification that enhances transcriptome diversity by changing RNA sequences.[1]
To profile the dynamic patterns of RNA editing during skeletal muscle development, we carried out strand-specific RNA sequencing (RNA-seq) in skeletal muscle across 27 developmental stages (SRA accession number SRP158448), including 15 prenatal and 12 postnatal stages, ranging from 33 days after conception to 180 days after birth
A whole genome sequencing (WGS) library (SRA accession number SRP157242), which was based on DNA isolated from the ear tissue of an adult male pig with the same genetic background as the pigs from which the samples were collected for RNA-seq, was sequenced
Summary
RNA editing represents a widespread post-transcriptional modification that enhances transcriptome diversity by changing RNA sequences.[1] The extensive application of next-generation sequencing has greatly facilitated the identification of RNA editing. An astonishingly large number of RNA editing sites have been confidently detected in humans, mice, and other species, demonstrating that RNA editing is pervasive in the genome.[2,3,4,5,6,7] Adenosine-to-inosine (A-to-I) RNA.
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