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Variability in porcine microRNA genes and its association with mRNA expression and lipid phenotypes

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dc.contributor.author Mármol-Sánchez, Emilio
dc.contributor.author Luigi-Sierra, María Gracia
dc.contributor.author Castelló, Anna
dc.contributor.author Guan, Dailu
dc.contributor.author Quintanilla, Raquel
dc.contributor.author Tonda, Raúl
dc.contributor.author Amills, Marcel
dc.date.accessioned 2021-07-08T07:58:30Z
dc.date.available 2021-07-08T07:58:30Z
dc.date.issued 2021
dc.identifier.citation Mármol-Sánchez E, Luigi-Sierra, MG, Castelló A, Guan D, Quintanilla R, Tonda R et al.Variability in porcine microRNA genes and its association with mRNA expression and lipid phenotypes. Genet Sel Evol. 2021 May 4;53(1):43. DOI: 10.1186/s12711-021-00632-3
dc.identifier.issn 0999-193X
dc.identifier.uri http://hdl.handle.net/10230/48113
dc.description.abstract Background: Mature microRNAs (miRNAs) play an important role in repressing the expression of a wide range of mRNAs. The presence of polymorphic sites in miRNA genes and their corresponding 3'UTR binding sites can disrupt canonical conserved miRNA-mRNA pairings, and thus modify gene expression patterns. However, to date such polymorphic sites in miRNA genes and their association with gene expression phenotypes and complex traits are poorly characterized in pigs. Results: By analyzing whole-genome sequences from 120 pigs and wild boars from Europe and Asia, we identified 285 single nucleotide polymorphisms (SNPs) that map to miRNA loci, and 109,724 SNPs that are located in predicted 7mer-m8 miRNA binding sites within porcine 3'UTR. In porcine miRNA genes, SNP density is reduced compared with their flanking non-miRNA regions. By sequencing the genomes of five Duroc boars, we identified 12 miRNA SNPs that were subsequently genotyped in their offspring (N = 345, Lipgen population). Association analyses of miRNA SNPs with 38 lipid-related traits and hepatic and muscle microarray expression phenotypes recorded in the Lipgen population were performed. The most relevant detected association was between the genotype of the rs319154814 (G/A) SNP located in the apical loop of the ssc-miR-326 hairpin precursor and PPP1CC mRNA levels in the liver (q-value = 0.058). This result was subsequently confirmed by qPCR (P-value = 0.027). The rs319154814 (G/A) genotype was also associated with several fatty acid composition traits. Conclusions: Our findings show a reduced variability of porcine miRNA genes, which is consistent with strong purifying selection, particularly in the seed region that plays a critical role in miRNA binding. Although it is generally assumed that SNPs mapping to the seed region are those with the most pronounced consequences on mRNA expression, we show that a SNP mapping to the apical region of ssc-miR-326 is significantly associated with hepatic mRNA levels of the PPP1CC gene, one of its predicted targets. Although experimental confirmation of such an interaction is reported in humans but not in pigs, this result highlights the need to further investigate the functional effects of miRNA polymorphisms that are located outside the seed region on gene expression in pigs.
dc.description.sponsorship The research presented in the current publication was funded by Grants AGL2013-48742-C2-1-R and AGL2013-48742-C2-2-R awarded by the Spanish Ministry of Economy and Competitivity. We also acknowledge the support of the Spanish Ministry of Science and Innovation for the Center of Excellence Severo Ochoa 2020–2023 (CEX2019-000902-S) grant awarded to the Centre for Research in Agricultural Genomics (CRAG, Bellaterra, Spain). Emilio Mármol-Sánchez was funded by a FPU Ph.D. grant from the Spanish Ministry of Education (FPU15/01733). María Gracia Luigi-Sierra was funded with a Ph.D. fellowship “Formación de Personal Investigador” (BES-C-2017-0024) awarded by the Spanish Ministry of Economy and Competitivity. Dailu Guan was funded by a Ph.D. fellowship from the Scholarship Council of China (CSC). The authors thank the CERCA Programme of the Generalitat de Catalunya (Barcelona, Spain) for their support and those who provided publicly available data
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher BioMed Central
dc.rights © Emilio Mármol-Sánchez et al 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made
dc.rights.uri https://creativecommons.org/licenses/by/4.0/
dc.subject.other Genètica
dc.subject.other Porcs
dc.title Variability in porcine microRNA genes and its association with mRNA expression and lipid phenotypes
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1186/s12711-021-00632-3
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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