Landscape of tissue-specific RNA Editome provides insight into co-regulated and altered gene expression in pigs (Sus-scrofa)

Adeyinka A Adetula; Xinhao Fan; Yongsheng Zhang; Yilong Yao; Junyu Yan; Muya Chen; Yijie Tang; Yuwen Liu; Guoqiang Yi; Kui Li; Zhonglin Tang

doi:10.1080/15476286.2021.1954380

Landscape of tissue-specific RNA Editome provides insight into co-regulated and altered gene expression in pigs (Sus-scrofa)

RNA Biol. 2021 Oct 15;18(sup1):439-450. doi: 10.1080/15476286.2021.1954380. Epub 2021 Jul 27.

Authors

Adeyinka A Adetula^{1

2

3

4}, Xinhao Fan^{1

2

4}, Yongsheng Zhang^{1

2

4}, Yilong Yao^{1

2

4}, Junyu Yan^{1

2

4}, Muya Chen^{1

2

4}, Yijie Tang^{1

2

4}, Yuwen Liu^{1

2

4

5

6}, Guoqiang Yi^{1

2

4

5

6}, Kui Li^{1

2

3}, Zhonglin Tang^{1

2

3

4

5

6}

Affiliations

¹ Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China.
² Genome Analysis Laboratory of the Ministry of Agriculture, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China.
³ Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.
⁴ Group of Pig Genome and Design Breeding, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China.
⁵ Kunpeng Institute of Modern Agriculture at Foshan, Foshan, China.
⁶ GuangXi Engineering Centre for Resource Development of Bama Xiang Pig, Bama, China.

Abstract

RNA editing generates genetic diversity in mammals by altering amino acid sequences, miRNA targeting site sequences, influencing the stability of targeted RNAs, and causing changes in gene expression. However, the extent to which RNA editing affect gene expression via modifying miRNA binding site remains unexplored. Here, we first profiled the dynamic A-to-I RNA editome across tissues of Duroc and Luchuan pigs. The RNA editing events at the miRNA binding sites were generated. The biological function of the differentially edited gene in skeletal muscle was further characterized in pig muscle-derived satellite cells. RNA editome analysis revealed a total of 171,909 A-to-I RNA editing sites (RESs), and examination of its features showed that these A-to-I editing sites were mainly located in SINE retrotransposons PRE-1/Pre0_SS element. Analysis of differentially edited sites (DESs) revealed a total of 4,552 DESs across tissues between Duroc and Luchuan pigs, and functional category enrichment analysis of differentially edited gene (DEG) sets highlighted a significant association and enrichment of tissue-developmental pathways including TGF-beta, PI3K-Akt, AMPK, and Wnt signaling pathways. Moreover, we found that RNA editing events at the miRNA binding sites in the 3'-UTR of HSPA12B mRNA could prevent the miRNA-mediated mRNA downregulation of HSPA12B in the muscle-derived satellite (MDS) cell, consistent with the results obtained from the Luchuan skeletal muscle. This study represents the most systematic attempt to characterize the significance of RNA editing in regulating gene expression, particularly in skeletal muscle, constituting a new layer of regulation to understand the genetic mechanisms behind phenotype variance in animals.Abbreviations: A-to-I: Adenosine-to-inosine; ADAR: Adenosine deaminase acting on RNA; RES: RNA editing site; DEG: Differentially edited gene; DES: Differentially edited site; FDR: False discovery rate; GO: Gene Ontology; KEGG: Kyoto Encyclopaedia of Genes and Genomes; MDS cell: musclederived satellite cell; RPKM: Reads per kilobase of exon model in a gene per million mapped reads; UTR: Untranslated coding regions.

Keywords: RNA editing; gene expression; hspa12b; miRNA; muscle-derived satellite cell; skeletal muscle.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3' Untranslated Regions / genetics*
Animals
Gene Expression Regulation*
MicroRNAs / genetics*
MicroRNAs / metabolism
Organ Specificity
RNA Editing*
RNA, Messenger / genetics*
RNA, Messenger / metabolism
Retroelements*
Swine

Substances

3' Untranslated Regions
MicroRNAs
RNA, Messenger
Retroelements

Grants and funding

This work was supported by the Key R&D Programmes of Guangdong Province (2018B020203003), the Basic and Applied Basic Research Foundation of Guangdong province (2019B1515120059), the National Natural Science Foundation of China (31830090), and the Agricultural Science and Technology Innovation Program (CAAS-ASTIP-ZDRW202006).