Dataset Information

Developmental atlas of the RNA editome in Sus scrofa skeletal muscle.

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.

SUBMITTER: Yang Y

PROVIDER: S-EPMC6589548 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Publications

Developmental atlas of the RNA editome in Sus scrofa skeletal muscle.

Yang Yalan Y Zhu Min M Fan Xinhao X Yao Yilong Y Yan Junyu J Tang Yijie Y Liu Siyuan S Li Kui K Tang Zhonglin Z

DNA research : an international journal for rapid publication of reports on genes and genomes 20190601 3

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 ...[more]

PMID: 31231762

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Project description:BACKGROUND:In animal breeding, identification of causative genetic variants is of major importance and high economical value. Usually, the number of candidate variants exceeds the number of variants that can be validated. One way of prioritizing probable candidates is by evaluating their potential to have a deleterious effect, e.g. by predicting their consequence. Due to experimental difficulties to evaluate variants that do not cause an amino-acid substitution, other prioritization methods are needed. For human genomes, the prediction of deleterious genomic variants has taken a step forward with the introduction of the combined annotation dependent depletion (CADD) method. In theory, this approach can be applied to any species. Here, we present pCADD (p for pig), a model to score single nucleotide variants (SNVs) in pig genomes. RESULTS:To evaluate whether pCADD captures sites with biological meaning, we used transcripts from miRNAs and introns, sequences from genes that are specific for a particular tissue, and the different sites of codons, to test how well pCADD scores differentiate between functional and non-functional elements. Furthermore, we conducted an assessment of examples of non-coding and coding SNVs, which are causal for changes in phenotypes. Our results show that pCADD scores discriminate between functional and non-functional sequences and prioritize functional SNVs, and that pCADD is able to score the different positions in a codon relative to their redundancy. Taken together, these results indicate that based on pCADD scores, regions with biological relevance can be identified and distinguished according to their rate of adaptation. CONCLUSIONS:We present the ability of pCADD to prioritize SNVs in the pig genome with respect to their putative deleteriousness, in accordance to the biological significance of the region in which they are located. We created scores for all possible SNVs, coding and non-coding, for all autosomes and the X chromosome of the pig reference sequence Sscrofa11.1, proposing a toolbox to prioritize variants and evaluate sequences to highlight new sites of interest to explain biological functions that are relevant to animal breeding.

Dataset Information

Developmental atlas of the RNA editome in Sus scrofa skeletal muscle.

Publications

Developmental atlas of the RNA editome in Sus scrofa skeletal muscle.

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