5.9
CiteScore
5.9
Impact Factor
Volume 50 Issue 6
Jun.  2023
Turn off MathJax
Article Contents

An atlas of expression quantitative trait loci of microRNAs in longissimus muscle of eight-way crossbred pigs

doi: 10.1016/j.jgg.2023.02.007
Funds:

We sincerely thank all the people from the State Key Laboratory for Pig Genetic Improvement and Production Technology (Jiangxi Agricultural University) for their help in sample and data collection. This study was supported by the National Natural Science Foundation of China (31790413 and 31872339).

  • Received Date: 2022-10-10
  • Accepted Date: 2023-02-05
  • Rev Recd Date: 2023-02-03
  • Publish Date: 2023-02-22
  • MicroRNAs (miRNAs) are key regulators of myocyte development and traits, yet insight into the genetic basis of variation in miRNA expression is still limited. Here, we present a systematic analysis of expression quantitative trait loci (eQTL) for miRNA profiling in longissimus muscle of pigs from an eight-breed crossed heterogeneous population. By integrating the whole-genome sequencing and miRNAomics data, we map 54 cis- and 292 trans-eQTLs at high resolution that are associated with the expression of 54 and 92 miRNAs, respectively. Twenty-three trans-acting loci are identified to affect the expression of nine myomiRs (known muscle-specific miRNAs). MiRNAs in mammalian conserved miRNA clusters are found to be subjected to regulation by shared cis-eQTLs, while the expression of mature miRNA-5p/-3p counterparts is more likely to be regulated by different cis-eQTLs. Fine mapping and bioinformatics analyses pinpoint the peak cis-eSNP of miR-4331-5p, rs344650810, which is located in its seed region, as a causal variant for the changes in expression and function of this miRNA. Additionally, rs344650810 is significantly (P < 0.01) correlated with the density and percentage of type I muscle fibers. Altogether, this study provides a comprehensive atlas of miRNA-eQTLs in porcine skeletal muscle and new insights into regulatory mechanisms of miRNA expression.
  • loading
  • [1]
    Ai, H., Fang, X., Yang, B., Huang, Z., Hao, C., Mao, L., Zhang, F., Zhang, L., Cui, L., He, W., et al., 2015. Adaptation and possible ancient interspecies introgression in pigs identified by whole-genome sequencing. Nat. Genet. 47, 217-225.
    [2]
    Albert, F.W., Kruglyak, L., 2015. The role of regulatory variation in complex traits and disease. Nat. Rev. Genet. 16, 197-212.
    [3]
    Almasy, L., Blangero, J., 1998. Multipoint quantitative-trait linkage analysis in general pedigrees. Am. J. Hum. Genet. 62, 1198-1211.
    [4]
    Browning, S.R., Browning, B.L., 2007. Rapid and accurate haplotype phasing and missing-data inference for whole-genome association studies by use of localized haplotype clustering. Am. J. Hum. Genet. 81, 1084-1097.
    [5]
    Borel, C., Deutsch, S., Letourneau, A., Migliavacca, E., Montgomery, S., Dimas, A., Vejnar, C., Attar, H., Gagnebin, M., Gehrig, C., et al., 2011. Identification of cis- and trans-regulatory variation modulating microRNA expression levels in human fibroblasts. Genome Res. 21, 68-73.
    [6]
    Budach, S., Heinig, M., Marsico, A., 2016. Principles of microRNA Regulation Revealed Through Modeling microRNA Expression Quantitative Trait Loci. Genetics 203, 1629-1640.
    [7]
    Bushati, N., Cohen, S.M., 2007. microRNA functions. Annu. Rev. Cell. Dev. Biol. 23, 175-205.
    [8]
    Chang, W., Fa, H., Xiao, D.,Wang, J., 2020. MicroRNA-184 alleviates insulin resistance in cardiac myocytes and high fat diet-induced cardiac dysfunction in mice through the LPP3/DAG pathway. Mol. Cell. Endocrinol. 508, 110793.
    [9]
    Chen, W., Larrabee, B.R., Ovsyannikova, I.G., Kennedy, R.B., Haralambieva, I.H., Poland, G.A., Schaid, D.J., 2015. Fine Mapping Causal Variants with an Approximate Bayesian Method Using Marginal Test Statistics. Genetics 200, 719-736.
    [10]
    Dai, F., Feng, D., Cao, Q., Ye, H., Zhang, C., Xia, W., Zuo, J., 2009. Developmental differences in carcass, meat quality and muscle fibre characteristics between the Landrace and a Chinese native pig. S. Afr. J. Anim. Sci. 39, 267-273.
    [11]
    Daza, K.R., Velez-Irizarry, D., Casiro, S., Steibel, J.P., Raney, N.E., Bates, R.O., Ernst, C.W., 2021. Integrated Genome-Wide Analysis of MicroRNA Expression Quantitative Trait Loci in Pig Longissimus Dorsi Muscle. Front. Genet. 12, 644091.
    [12]
    Delaneau, O., Ongen, H., Brown, A.A., Fort, A., Panousis, N.I., Dermitzakis, E.T., 2017. A complete tool set for molecular QTL discovery and analysis. Nat. Commun. 8, 15452.
    [13]
    DeVeale, B., Swindlehurst-Chan, J., Blelloch, R., 2021. The roles of microRNAs in mouse development. Nat. Rev. Genet. 22, 307-323.
    [14]
    Dodt, M., Roehr, J., Ahmed, R., Dieterich, C., 2012. FLEXBAR-Flexible Barcode and Adapter Processing for Next-Generation Sequencing Platforms. Biology 1, 895-905.
    [15]
    Dong, S.S., He, W.M., Ji, J.J., Zhang, C., Guo, Y., Yang, T.L., 2021. LDBlockShow: a fast and convenient tool for visualizing linkage disequilibrium and haplotype blocks based on variant call format files. Brief. Bioinform. 22, 1-6.
    [16]
    Friedlander, M.R., Mackowiak, S.D., Li, N., Chen, W., Rajewsky, N., 2012. miRDeep2 accurately identifies known and hundreds of novel microRNA genes in seven animal clades. Nucleic Acids Res. 40, 37-52.
    [17]
    Fu, A., Hoffman, A.E., Liu, R., Jacobs, D.I., Zheng, T., Zhu, Y., 2014. Targetome profiling and functional genetics implicate miR-618 in lymphomagenesis. Epigenetics 9, 730-737.
    [18]
    Gamazon, E.R., Innocenti, F., Wei, R., Wang, L., Zhang, M., Mirkov, S., Ramirez, J., Huang, R.S., Cox, N.J., Ratain, M.J., et al., 2013. A genome-wide integrative study of microRNAs in human liver. BMC Genomics 14, 395.
    [19]
    Gamazon, E.R., Ziliak, D., Im, H.K., LaCroix, B., Park, D.S., Cox, N.J., Huang, R.S., 2012. Genetic architecture of microRNA expression: implications for the transcriptome and complex traits. Am. J. Hum. Genet. 90, 1046-1063.
    [20]
    Gil, M., Delday, M., Gispert, M., I Furnols, M., Maltin, C., Plastow, G., Klont, R., Sosnicki, A., Carrion, D., 2008. Relationships between biochemical characteristics and meat quality of Longissimus thoracis and Semimembranosus muscles in five porcine lines. Meat Sci. 80, 927-933.
    [21]
    Gong, J., Tong, Y., Zhang, H.M., Wang, K., Hu, T., Shan, G., Sun, J., Guo, A.Y., 2012. Genome-wide identification of SNPs in microRNA genes and the SNP effects on microRNA target binding and biogenesis. Hum. Mutat. 33, 254-263.
    [22]
    Haas, J., Mester, S., Lai, A., Frese, K.S., Sedaghat-Hamedani, F., Kayvanpour, E., Rausch, T., Nietsch, R., Boeckel, J.N., Carstensen, A., et al., 2018. Genomic structural variations lead to dysregulation of important coding and non-coding RNA species in dilated cardiomyopathy. EMBO Mol. Med. 10, 107-120.
    [23]
    Hormozdiari, F., Gazal, S., van de Geijn, B., Finucane, H.K., Ju, C.J., Loh, P.R., Schoech, A., Reshef, Y., Liu, X., O'Connor, L., et al., 2018. Leveraging molecular quantitative trait loci to understand the genetic architecture of diseases and complex traits. Nat. Genet. 50, 1041-1047.
    [24]
    Huan, T., Rong, J., Liu, C., Zhang, X., Tanriverdi, K., Joehanes, R., Chen, B.H., Murabito, J.M., Yao, C., Courchesne, P., et al., 2015. Genome-wide identification of microRNA expression quantitative trait loci. Nat. Commun. 6, 6601.
    [25]
    Huang, J., Li, X., Li, H., Su, Z., Wang, J., Zhang, H., 2015. Down-regulation of microRNA-184 contributes to the development of cyanotic congenital heart diseases. Int. J. Clin. Exp. Pathol. 8, 14221-14227.
    [26]
    Huang, Y., Cai, L., Duan, Y., Zeng, Q., He, M., Wu, Z., Zou, X., Zhou, M., Zhang, Z., Xiao, S., et al., 2022. Whole-genome sequence-based association analyses on an eight-breed cro ssed heterogeneous stock of pigs reveal the genetic basis of skeletal muscle fiber characteristics. Meat Sci. 194, 108974.
    [27]
    Huang, Y., Zhou, L., Zhang, J., Liu, X., Zhang, Y., Cai, L., Zhang, W., Cui, L., Yang, J., Ji, J., et al., 2020. A large-scale comparison of meat quality and intramuscular fatty acid composition among three Chinese indigenous pig breeds. Meat Sci. 168, 108182.
    [28]
    Ji, J., Zhou, L., Huang, Y., Zheng, M., Liu, X., Zhang, Y., Huang, C., Peng, S., Zeng, Q., Zhong, L., et al., 2018. A whole-genome sequence based association study on pork eating quality traits and cooking loss in a specially designed heterogeneous F6 pig population. Meat Sci. 146, 160-167.
    [29]
    Kern, C., Wang, Y., Xu, X., Pan, Z., Halstead, M., Chanthavixay, G., Saelao, P., Waters, S., Xiang, R., Chamberlain, A., et al., 2021. Functional annotations of three domestic animal genomes provide vital resources for comparative and agricultural research. Nat. Commun. 12, 1821.
    [30]
    Lappalainen, T., Sammeth, M., Friedlander, M.R., t Hoen, P.A., Monlong, J., Rivas, M.A., Gonzalez-Porta, M., Kurbatova, N., Griebel, T., Ferreira, P.G., et al., 2013. Transcriptome and genome sequencing uncovers functional variation in humans. Nature 501, 506-511.
    [31]
    Lee, J.S., Kim, J.M., Lim, K.S., Hong, J.S., Hong, K.C.,Lee, Y.S., 2013. Effects of polymorphisms in the porcine microRNA MIR206/MIR133B cluster on muscle fiber and meat quality traits. Anim. Genet. 44, 101-106.
    [32]
    Li, H., Durbin, R., 2010. Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics 26, 589-595.
    [33]
    Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., Durbin, R., et al., S., 2009. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25, 2078-2079.
    [34]
    Martin, M., 2011. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet J. 17, 1.
    [35]
    Miao, W., Ma, Z., Tang, Z., Yu, L., Liu, S., Huang, T., Wang, P., Wu, T., Song, Z., Zhang, H., et al., 2021. Integrative ATAC-seq and RNA-seq Analysis of the Longissimus Muscle of Luchuan and Duroc Pigs. Front. Nutr. 8, 742672.
    [36]
    Mok, G.F., Lozano-Velasco, E., Munsterberg, A., 2017. microRNAs in skeletal muscle development. Semin. Cell Dev. Biol. 72, 67-76.
    [37]
    Nikpay, M., Beehler, K., Valsesia, A., Hager, J., Harper, M.E., Dent, R., McPherson, R., 2019. Genome-wide identification of circulating-miRNA expression quantitative trait loci reveals the role of several miRNAs in the regulation of cardiometabolic phenotypes. Cardiovasc. Res. 115, 1629-1645.
    [38]
    Ponsuksili, S., Murani, E., Hadlich, F., Perdomo-Sabogal, A., Trakooljul, N., Oster, M., Reyer, H., Wimmers, K., 2022. Genetic regulation and variation of expression of miRNA and mRNA transcripts in fetal muscle tissue in the context of sex, dam and variable fetal weight. Biol. Sex. Differ. 13, 24.
    [39]
    Ponsuksili, S., Oster, M., Reyer, H., Hadlich, F., Trakooljul, N., Rodehutscord, M., Camarinha-Silva, A., Bennewitz, J., Wimmers, K., 2021. Genetic regulation and heritability of miRNA and mRNA expression link to phosphorus utilization and gut microbiome. Open Biol. 11, 200182.
    [40]
    Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M., Bender, D., Maller, J., Sklar, P., de Bakker, P., Daly, M., et al., 2007. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559-575.
    [41]
    Rimmer, A., Phan, H., Mathieson, I., Iqbal, Z., Twigg, S.R.F., Consortium, W.G.S., Wilkie, A.O.M., McVean, G., Lunter, G., 2014. Integrating mapping-, assembly- and haplotype-based approaches for calling variants in clinical sequencing applications. Nat. Genet. 46, 912-918.
    [42]
    Siengdee, P., Trakooljul, N., Murani, E., Brand, B., Schwerin, M., Wimmers, K., Ponsuksili, S., 2015. Pre- and post-natal muscle microRNA expression profiles of two pig breeds differing in muscularity. Gene 561, 190-198.
    [43]
    Sonehara, K., Sakaue, S., Maeda, Y., Hirata, J., Kishikawa, T., Yamamoto, K., Matsuoka, H., Yoshimura, M., Nii, T., Ohshima, S., et al., 2022. Genetic architecture of microRNA expression and its link to complex diseases in the Japanese population. Hum. Mol. Genet. 31, 1806-1820.
    [44]
    Tan, G.G., Xu, C., Zhong, W.K., Wang, C.Y., 2021. miR-184 delays cell proliferation, migration and invasion in prostate cancer by directly suppressing DLX1. Exp. Ther. Med. 22, 1163.
    [45]
    Wang, J., Yang, X., Sun, Q., Huang, R., Xing, Z., 2011. Maternal dietary protein induces opposite myofiber type transition in Meishan pigs at weaning and finishing stages. Meat Sci. 2011,89(2), 221-227.
    [46]
    Wu, Z., Gong, H., Zhou, Z., Jiang, T., Lin, Z., Li, J., Xiao, S., Yang, B., Huang, L., 2022. Mapping short tandem repeats for liver gene expression traits helps prioritize potential causal variants for complex traits in pigs. J. Anim. Sci. Biotechnol. 13, 8.
    [47]
    Yang, H., Wu, J., Huang, X., Zhou, Y., Zhang, Y., Liu, M., Liu, Q., Ke, S., He, M., Fu, H., et al., 2022. ABO genotype alters the gut microbiota by regulating GalNAc levels in pigs. Nature 606, 358-367.
    [48]
    Yang, J., Lee, S.H., Goddard, M.E., Visscher, P.M., 2011. GCTA: a tool for genome-wide complex trait analysis. Am. J. Hum. Genet. 88, 76-82.
    [49]
    Zhang, J., Chen, J., Liu, X., Wang, H., Liu, X., Li, X., Wu, Z., Zhu, M., Zhao, S., 2016. Genomewide association studies for hematological traits and T lymphocyte subpopulations in a Duroc x Erhualian F resource population. J. Anim. Sci. 94, 5028-5041.
    [50]
    Zhang, J., Liu,Y., 2017a. MicroRNA in Skeletal Muscle: Its Crucial Roles in Signal Proteins, Mus cle Fiber Type, and Muscle Protein Synthesis. Curr. Protein. Pept. Sci. 18, 579-588.
    [51]
    Zhang, S., Wang, R., Su, H., Wang, B., Suolang, S., Lei, Z., Jin, M., Chen, H., Cao, J., Zhou, H., 2017b. Sus scrofa miR-204 and miR-4331 Negatively Regulate Swine H1N1/2009 Influenza A Virus Replication by Targeting Viral HA and NS, Respectively. Int. J. Mol. Sci. 18, 749.
    [52]
    Zhao, X., Bai, X., Guan, L., Li, J., Song, X., Ma, X., Guo, J., Zhang, Z., Qian, D.,Yong, H., 2018. microRNA-4331 Promotes Transmissible Gastroenteritis Virus (TGEV)-induced Mitochondrial Damage Via Targeting RB1, Upregulating Interleukin-1 Receptor Accessory Protein (IL1RAP), and Activating p38 MAPK Pathway In Vitro. Mol. Cell. Proteomics 17, 190-204.
    [53]
    Zhou, Y., Zhou, B., Pache, L., Chang, M., Khodabakhshi, A.H., Tanaseichuk, O., Benner, C., Chanda, S.K., 2019. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat. Commun. 10, 1523.
    [54]
    Zilahi, E., Adamecz, Z., Bodoki, L., Griger, Z., Poliska, S., Nagy-Vincze, M., Danko, K., 2019. Dysregulated expression profile of myomiRs in the skeletal muscle of patients with polymyositis. EJIFCC 30, 237-245.
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Article Metrics

    Article views (230) PDF downloads (21) Cited by ()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return