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RNA editing modifying RNA bases in a post-transcriptional process has been extensively studied for model animals. However, less evidence is available that RNA editing plays a role in the development of metabolic disorders. Here, we profiled the A-to-I editing in three tissues and six gut segments and characterized the functional aspect of editing sites in model pigs for metabolic disorders. We detected 64,367 non-redundant A-to-I editing sites across the pig genome, and 20.1% correlated with their located genes\u2019 expression. The largest number of A-to-I sites was found in the abdominal aorta with the highest editing levels. The significant difference in editing levels between high-energy induced and control pigs was detected in the abdominal aorta, testis, duodenum, ileum, colon, and cecum. We next focused on 6041 functional A-to-I sites that detected differences or specificity between treatments. We found functional A-to-I sites specifically involved in a tissue-specific manner. Two of them, located in gene SLA-DQB1 and near gene B4GALT5 were found to be shared by three tissues and six gut segments. Although we did not find them enriched in each of the gene features, in correlation analysis, we noticed that functional A-to-I sites were significantly enriched in gene 3\u2032-UTRs. This result indicates, in general, A-to-I editing has the largest potential in the regulation of gene expression through changing the 3\u2032-UTRs\u2019 sequence, which is functionally involved in pigs under a long-term high-energy diet. Our work provides valuable knowledge of A-to-I editing sites functionally involved in the development of the metabolic disorder.<\/jats:p>","DOI":"10.3390\/ijms24097921","type":"journal-article","created":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T04:30:47Z","timestamp":1682569847000},"page":"7921","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Characterization of A-to-I Editing in Pigs under a Long-Term High-Energy Diet"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4179-8587","authenticated-orcid":false,"given":"Liu","family":"Yang","sequence":"first","affiliation":[{"name":"Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Key Laboratory of Livestock and Poultry Multi-Omics of MARA, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518124, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Huang","sequence":"additional","affiliation":[{"name":"Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Key Laboratory of Livestock and Poultry Multi-Omics of MARA, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518124, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulian","family":"Mu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs of China, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kui","family":"Li","sequence":"additional","affiliation":[{"name":"Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Key Laboratory of Livestock and Poultry Multi-Omics of MARA, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518124, China"},{"name":"State Key Laboratory of Animal Nutrition and Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs of China, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1073\/pnas.98.3.805","article-title":"The universal nature of biochemistry","volume":"98","author":"Pace","year":"2001","journal-title":"Proc. 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