Dataset Information

Co-Expression Networks Reveal Potential Regulatory Roles of miRNAs in Fatty Acid Composition of Nelore Cattle.

ABSTRACT: Fatty acid (FA) content affects the sensorial and nutritional value of meat and plays a significant role in biological processes such as adipogenesis and immune response. It is well known that, in beef, the main FAs associated with these biological processes are oleic acid (C18:1 cis9, OA) and conjugated linoleic acid (CLA-c9t11), which may have beneficial effects on metabolic diseases such as type 2 diabetes and obesity. Here, we performed differential expression and co-expression analyses, weighted gene co-expression network analysis (WGCNA) and partial correlation with information theory (PCIT), to uncover the complex interactions between miRNAs and mRNAs expressed in skeletal muscle associated with FA content. miRNA and mRNA expression data were obtained from skeletal muscle of Nelore cattle that had extreme genomic breeding values for OA and CLA. Insulin and MAPK signaling pathways were identified by WGCNA as central pathways associated with both of these fatty acids. Co-expression network analysis identified bta-miR-33a/b, bta-miR-100, bta-miR-204, bta-miR-365-5p, bta-miR-660, bta-miR-411a, bta-miR-136, bta-miR-30-5p, bta-miR-146b, bta-let-7a-5p, bta-let-7f, bta-let-7, bta-miR 339, bta-miR-10b, bta-miR 486, and the genes ACTA1 and ALDOA as potential regulators of fatty acid synthesis. This study provides evidence and insights into the molecular mechanisms and potential target genes involved in fatty acid content differences in Nelore beef cattle, revealing new candidate pathways of phenotype modulation that could positively benefit beef production and human consumption.

SUBMITTER: de Oliveira PSN

PROVIDER: S-EPMC6637853 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Co-Expression Networks Reveal Potential Regulatory Roles of miRNAs in Fatty Acid Composition of Nelore Cattle.

de Oliveira Priscila S N PSN Coutinho Luiz L LL Cesar Aline S M ASM Diniz Wellison J da Silva WJDS de Souza Marcela M MM Andrade Bruno G BG Koltes James E JE Mourão Gerson B GB Zerlotini Adhemar A Reecy James M JM Regitano Luciana C A LCA

Frontiers in genetics 20190711

Fatty acid (FA) content affects the sensorial and nutritional value of meat and plays a significant role in biological processes such as adipogenesis and immune response. It is well known that, in beef, the main FAs associated with these biological processes are oleic acid (C18:1 cis9, OA) and conjugated linoleic acid (CLA-c9t11), which may have beneficial effects on metabolic diseases such as type 2 diabetes and obesity. Here, we performed differential expression and co-expression analyses, wei ...[more]

PMID: 31354792

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Project description:BackgroundPositively correlated with carcass weight and animal growth, the ribeye area (REA) and the backfat thickness (BFT) are economic important carcass traits, which impact directly on producer's payment. The selection of these traits has not been satisfactory since they are expressed later in the animal's life and multigene regulated. So, next-generation technologies have been applied in this area to improve animal's selection and better understand the molecular mechanisms involved in the development of these traits. Correlation network analysis, performed by tools like WGCNA (Weighted Correlation Network Analysis), has been used to explore gene-gene interactions and gene-phenotype correlations. Thus, this study aimed to identify putative candidate genes and metabolic pathways that regulate REA and BFT by constructing a gene co-expression network using WGCNA and RNA sequencing data, to better understand genetic and molecular variations behind these complex traits in Nelore cattle.ResultsThe gene co-expression network analysis, using WGCNA, were built using RNA-sequencing data normalized by transcript per million (TPM) from 43 Nelore steers. Forty-six gene clusters were constructed, between them, three were positively correlated (p-value< 0.1) to the BFT (Green Yellow, Ivory, and Light Yellow modules) and, one cluster was negatively correlated (p-value< 0.1) with REA (Salmon module). The enrichment analysis performed by DAVID and WebGestalt (FDR 5%) identified eight Gene Ontology (GO) terms and three KEGG pathways in the Green Yellow module, mostly associated with immune response and inflammatory mechanisms. The enrichment of the Salmon module demonstrated 19 GO terms and 21 KEGG pathways, related to muscle energy metabolism, lipid metabolism, muscle degradation, and oxidative stress diseases. The Ivory and Light yellow modules have not shown significant results in the enrichment analysis.ConclusionWith this study, we verified that inflammation and immune response pathways modulate the BFT trait. Energy and lipid metabolism pathways, highlighting fatty acid metabolism, were the central pathways associated with REA. Some genes, as RSAD2, EIF2AK2, ACAT1, and ACSL1 were considered as putative candidate related to these traits. Altogether these results allow us to a better comprehension of the molecular mechanisms that lead to muscle and fat deposition in bovine.

Project description:BackgroundThe amount of intramuscular fat can influence the sensory characteristics and nutritional value of beef, thus the selection of animals with adequate fat deposition is important to the consumer. There is growing knowledge about the genes and pathways that control the biological processes involved in fat deposition in muscle. MicroRNAs (miRNAs) belong to a well-conserved class of non-coding small RNAs that modulate gene expression across a range of biological functions in animal development and physiology. The aim of this study was to identify differentially expressed (DE) miRNAs, regulatory candidate genes and co-expression networks related to intramuscular fat (IMF) deposition. To achieve this, we used mRNA and miRNA expression data from the Longissimus dorsi muscle of 30 Nelore steers with high (H) and low (L) genomic estimated breeding values (GEBV) for IMF deposition.ResultsDifferential miRNA expression analysis between animals with extreme GEBV values for IMF identified six DE miRNAs (FDR 10%). Functional annotation of the target genes for these microRNAs indicated that the PPARs signaling pathway is involved with IMF deposition. Candidate regulatory genes such as SDHAF4, FBXO17, ALDOA and PKM were identified by partial correlation with information theory (PCIT), phenotypic impact factor (PIF) and regulatory impact factor (RIF) co-expression approaches from integrated miRNA-mRNA expression data. Two DE miRNAs (FDR 10%), bta-miR-143 and bta-miR-146b, which were upregulated in the Low IMF group, were correlated with regulatory candidate genes, which were functionally enriched for fatty acid oxidation GO terms. Co-expression patterns obtained by weighted correlation network analysis (WGCNA), which showed possible interaction and regulation between mRNAs and miRNAs, identified several modules related to immune system function, protein metabolism, energy metabolism and glucose catabolism according to in silico analysis performed herein.ConclusionIn this study, several genes and miRNAs were identified as candidate regulators of IMF by analyzing DE miRNAs using two different miRNA-mRNA co-expression network methods. This study contributes to the understanding of potential regulatory mechanisms of gene signaling networks involved in fat deposition processes measured in muscle. Glucose metabolism and inflammation processes were the main pathways found in silico to influence intramuscular fat deposition in beef cattle in the integrative mRNA-miRNA co-expression analysis.

Project description:Puberty is a complex physiological event by which animals mature into an adult capable of sexual reproduction. In order to enhance our understanding of the genes and regulatory pathways and networks involved in puberty, we characterized the transcriptome of five reproductive tissues (i.e. hypothalamus, pituitary gland, ovary, uterus, and endometrium) as well as tissues known to be relevant to growth and metabolism needed to achieve puberty (i.e., longissimus dorsi muscle, adipose, and liver). These tissues were collected from pre- and post-pubertal Brangus heifers (3/8 Brahman; Bos indicus x 5/8 Angus; Bos taurus) derived from a population of cattle used to identify quantitative trait loci associated with fertility traits (i.e., age of first observed corpus luteum (ACL), first service conception (FSC), and heifer pregnancy (HPG)). In order to exploit the power of complementary omics analyses, pre- and post-puberty co-expression gene networks were constructed by combining the results from genome-wide association studies (GWAS), RNA-Seq, and bovine transcription factors. Eight tissues among pre-pubertal and post-pubertal Brangus heifers revealed 1,515 differentially expressed and 943 tissue-specific genes within the 17,832 genes confirmed by RNA-Seq analysis. The hypothalamus experienced the most notable up-regulation of genes via puberty (i.e., 204 out of 275 genes). Combining the results of GWAS and RNA-Seq, we identified 25 loci containing a single nucleotide polymorphism (SNP) associated with ACL, FSC, and (or) HPG. Seventeen of these SNP were within a gene and 13 of the genes were expressed in uterus or endometrium. Multi-tissue omics analyses revealed 2,450 co-expressed genes relative to puberty. The pre-pubertal network had 372,861 connections whereas the post-pubertal network had 328,357 connections. A sub-network from this process revealed key transcriptional regulators (i.e., PITX2, FOXA1, DACH2, PROP1, SIX6, etc.). Results from these multi-tissue omics analyses improve understanding of the number of genes and their complex interactions for puberty in cattle.

Dataset Information

Co-Expression Networks Reveal Potential Regulatory Roles of miRNAs in Fatty Acid Composition of Nelore Cattle.

Publications

Co-Expression Networks Reveal Potential Regulatory Roles of miRNAs in Fatty Acid Composition of Nelore Cattle.

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