Developmental atlas of the RNA editome in Sus scrofa skeletal muscle

Yang, Yalan; Zhu, Min; Fan, Xinhao; Yao, Yilong; Yan, Junyu; Tang, Yijie; Liu, Siyuan; Li, Kui; Tang, Zhonglin

doi:10.1093/dnares/dsz006

Cited by 22 publications

(41 citation statements)

References 61 publications

(84 reference statements)

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“…Previous studies suggested that A-to-I RNA editing might disturb the existing miRNA binding or generate novel miRNA binding [5,13,39]. The results of the present study showed that the A-to-I editing of 143 DESs might affect the binding ability of miRNA.…”

Section: Discussionsupporting

confidence: 45%

“…The RNA editing sites in PG were identified using a previously published pipeline [13]. This pipeline was modified based on previous studies in other species [9,10,12,[25][26][27] and has been proved to be efficient and solid for the accurately identification of high-confidence RNA editing in pigs [13]. Briefly, the variants called by the transcriptome data were filtered by the following steps:…”

Section: Rna Editing Detectionmentioning

confidence: 99%

“…The results identified more than a hundred million RNA editing sites in mammalian genomes and on the majority of genes [ 12 ]. Several studies have recently identified and reported the characteristics of RNA editing in the genome of pigs, a major source of meat and an ideal biomedical model [ 13 – 16 ]. For example, the RNA editome in the pig skeletal muscle across 27 developmental stages showed that the overall editing level decreased throughout development and RNA editing is a vital regulator of myogenesis and muscle development [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…Several studies have recently identified and reported the characteristics of RNA editing in the genome of pigs, a major source of meat and an ideal biomedical model [ 13 – 16 ]. For example, the RNA editome in the pig skeletal muscle across 27 developmental stages showed that the overall editing level decreased throughout development and RNA editing is a vital regulator of myogenesis and muscle development [ 13 ]. These studies provide rich resources for a better understanding of the functions and mechanisms of RNA editing during various biological processes.…”

Section: Introductionmentioning

confidence: 99%

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Developmental stage-specific A-to-I editing pattern in the postnatal pineal gland of pigs (Sus scrofa)

Zhou

Wang

Xie

et al. 2020

J Animal Sci Biotechnol

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Background: RNA editing is a widespread post-transcriptional modification mechanism in mammalian genomes. Although many editing sites have been identified in domestic pigs (Sus scrofa), little is known about the characteristics and dynamic regulation of RNA editing in the pineal gland (PG), a small neuroendocrine gland that synthesizes and secretes melatonin, which is primarily responsible to modulate sleep patterns. Results: This study analyzed the expression of adenosine-to-inosine (A-to-I) editing regulators and profiled the first dynamic A-to-I RNA editome during postnatal PG development. The results identified ADAR1 as the most abundantly expressed ADAR enzyme, which was down-regulated during postnatal PG development. Furthermore, 47,284 high-confidence RNA editing sites were identified, the majority of which (93.6%) were of the canonical A-to-I editing type, followed by C-toT editing. Analysis of its characteristics showed that the A-to-I editing sites mostly localized in SINE retrotransposons PRE-1/Pre0_SS. Moreover, a strong deficiency and preference for guanine nucleotides at positions of one base upstream or downstream were found, respectively. The overall editing level at the puberty stage was higher than at both infancy and adulthood stages. Additionally, genome-wide RNA editing was found to exhibit a dynamic stage-specific fashion (postnatally). Genes that underwent developmental changes in RNA editing were associated with catabolic processes as well as protein localization and transport functions, implying that RNA editing might be responsible for the molecular machineries of the postnatal developing PG. Remarkably, RNA editing in 3′-UTRs might regulate gene expression by influencing miRNA binding during PG development. Conclusions: This study profiles the first comprehensive developmental RNA editome in the pig PG, which contributes to the understanding of the importance of post-transcriptionally mediated regulation during mammalian postnatal PG development. Moreover, this study widely extends RNA editome resources in mammals.

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Section: Discussionsupporting

confidence: 45%

Section: Rna Editing Detectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Developmental stage-specific A-to-I editing pattern in the postnatal pineal gland of pigs (Sus scrofa)

Zhou

Wang

Xie

et al. 2020

J Animal Sci Biotechnol

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“…These findings imply that SPPL2A, which participates in the immune response, may be specially activated through RNA editing mechanisms, when Gram-negative bacteria infect different types of tissues. Comparing our results with the atlas of the RNA editome in Sus scrofa skeletal muscle [78], we confirmed 22 of 57 RNA editing sites expressed in the endometrial tissues. Significant AAF changes in 3 UTR TMEM161A and upstream from GFM1 could be linked with the potential mechanism of implantation failure [79] and intrauterine growth retardation [80], respectively.…”

Section: Discussionsupporting

confidence: 75%

Transcriptome, Spliceosome and Editome Expression Patterns of the Porcine Endometrium in Response to a Single Subclinical Dose of Salmonella Enteritidis Lipopolysaccharide

Paukszto

Mikołajczyk

Jastrzebski

et al. 2020

IJMS

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Endometrial infections at a young age can lead to fertility issues in adulthood. Bacterial endotoxins, such as lipopolysaccharide (LPS), can participate in long-term molecular changes even at low concentrations. Lipopolysaccharide plays a crucial role in the progression of septic shock, inflammation and auto-immune diseases. The aim of this study was to describe transcriptomic modulations in the porcine endometrium, induced in vivo by a single subclinical dose of LPS from Salmonella Enteritidis. which did not produce clinical symptoms of toxicity. The RNA-seq methodology was applied to reveal 456 differentially expressed regions, including 375 genes, four long noncoding RNAs, and 77 other unclassified transcripts. Two independent methods confirmed 118 alternatively spliced genes that participate i.a., in the formation of the MHC-I complex and the adaptive immune response. Single nucleotide variant-calling algorithms supported the identification of 3730 allele-specific expression variants and 57 canonical A-to-I RNA editing sites. The results demonstrated that the differential expression of genes involved in inflammation, immune response, angiogenesis and endometrial development may be maintained for up to 7 days after exposure to LPS. RNA editing sites and long noncoding RNAs (lncRNAs) play an important role in transcriptional regulatory machinery in the porcine endometrium in response to LPS administration.

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circRNAome profiling reveals circFgfr2 regulates myogenesis and muscle regeneration via a feedback loop

Yan

Yang

Fan

et al. 2021

J cachexia sarcopenia muscle

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Background Circular RNAs (circRNAs) represent a novel class of non‐coding RNAs formed by a covalently closed loop and play crucial roles in many biological processes. Several circRNAs associated with myogenesis have been reported. However, the dynamic expression, function, and mechanism of circRNAs during myogenesis and skeletal muscle development are largely unknown. Methods Strand‐specific RNA‐sequencing (RNA‐seq) and microarray datasets were used to profile the dynamic circRNAome landscape during skeletal muscle development and myogenic differentiation. Bioinformatics analyses were used to characterize the circRNAome and identify candidate circRNAs associated with myogenesis. Bulk and single‐cell RNA‐seq were performed to identify the downstream genes and pathways of circFgfr2. The primary myoblast cells, C2C12 cells, and animal model were used to assess the function and mechanism of circFgfr2 in myogenesis and muscle regeneration in vitro or in vivo by RT‐qPCR, western blotting, dual‐luciferase activity assay, RNA immunoprecipitation, RNA fluorescence in situ hybridization, and chromatin immunoprecipitation. Results We profiled the dynamic circRNAome in pig skeletal muscle across 27 developmental stages and detected 52 918 high‐confidence circRNAs. A total of 2916 of these circRNAs are conserved across human, mouse, and pig, including four circRNAs (circFgfr2, circQrich1, circMettl9, and circCamta1) that were differentially expressed (|log2 fold change| > 1 and adjusted P value < 0.05) in various myogenesis systems. We further focused on a conserved circRNA produced from the fibroblast growth factor receptor 2 (Fgfr2) gene, termed circFgfr2, which was found to inhibit myoblast proliferation and promote differentiation and skeletal muscle regeneration. Mechanistically, circFgfr2 acted as a sponge for miR‐133 to regulate the mitogen‐activated protein kinase kinase kinase 20 (Map3k20) gene and JNK/MAPK pathway. Importantly, transcription factor Kruppel like factor 4 (Klf4), the downstream target of the JNK/MAPK pathway, directly bound to the promoter of circFgfr2 and affected its expression via an miR‐133/Map3k20/JNK/Klf4 auto‐regulatory feedback loop. RNA binding protein G3BP stress granule assembly factor 1 (G3bp1) inhibited the biogenesis of circFgfr2. Conclusions The present study provides a comprehensive circRNA resource for skeletal muscle study. The functional and mechanistic analysis of circFgfr2 uncovered a circRNA‐mediated auto‐regulatory feedback loop regulating myogenesis and muscle regeneration, which provides new insight to further understand the regulatory mechanism of circRNAs.

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Developmental atlas of the RNA editome in Sus scrofa skeletal muscle

Cited by 22 publications

References 61 publications

Developmental stage-specific A-to-I editing pattern in the postnatal pineal gland of pigs (Sus scrofa)

Developmental stage-specific A-to-I editing pattern in the postnatal pineal gland of pigs (Sus scrofa)

Transcriptome, Spliceosome and Editome Expression Patterns of the Porcine Endometrium in Response to a Single Subclinical Dose of Salmonella Enteritidis Lipopolysaccharide

circRNAome profiling reveals circFgfr2 regulates myogenesis and muscle regeneration via a feedback loop

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