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

Abstract

25 Background 26 Mature microRNAs (miRNAs) play an important role in repressing the expression of a 27 wide range of protein coding transcripts by promoting their degradation or inhibiting 28 their translation into functional proteins. The presence of segregating polymorphisms 29 inside miRNA loci and their corresponding 3'UTR binding sites might disrupt canonical 30 conserved miRNA-mRNA pairing, thus modifying gene expression patterns. 31 Results 32We aimed to investigate the variability of miRNA genes and their putative binding sites 33 by analyzing whole-genome sequences from 120 pigs and wild boars from Europe and 34 Asia. In total, 285 SNPs residing within miRNA loci were detected. From these, 221 35 were located in precursor regions, whereas 52 and 12 mapped to mature and seed 36 regions, respectively. Moreover, a total of 109,724 polymorphisms were identified in 37 predicted 7mer-m8 miRNA binding sites within porcine 3'UTRs. A principal 38 components analysis revealed a clear genetic divergence between Asian and European 39 samples, which was particularly strong for 3'UTR sequences. We also observed that 40 miRNA genes show reduced polymorphism compared with other non-miRNA regions. 41To assess the potential consequences of miRNA polymorphisms, we sequenced the 42 genomes of 5 Duroc pigs and, by doing so, we identified 15 miRNA SNPs that were 43 genotyped in the offspring (N = 345) of the five boars. Association analyses between 44 miRNA SNPs and hepatic and muscle microarray data allowed us to identify 4 45 polymorphisms displaying significant associations. Particularly interesting was the 46 rs319154814 polymorphism (G/A), located in the apical loop of the ssc-miR-326 47 3 precursor sequence. This polymorphism is predicted to cause a subtle hairpin 48 rearrangement that improves the accessibility to processing enzymatic factors. 49 Conclusions 50 Porcine miRNA genes show a reduced variability, particularly in the seed region which 51 plays a critical role in miRNA binding. Although it is generally assumed that SNPs 52 mapping to the seed region are the ones with the strongest consequences on mRNA 53 expression, we show that a SNP mapping to the apical region of ssc-miR-326 is 54 associated with the mRNA expression of several of its predicted targets. This result 55 suggests that porcine miRNA variability mapping within and outside the seed region 56 could have important regulatory effects on gene expression. 57 58 59 60 61 62 63 64 65 66 67 4 Background 68 Mature microRNA transcripts (miRNAs) are short (~22 nt) non-coding RNAs 69 which play an essential role in the regulation of gene expression [1]. During the 70 biogenesis of miRNAs, one strand of the miRNA duplex binds to the guide-strand 71 channel of an Argonaute protein forming an miRNA-induced silencing complex 72 (miRISC) with the ability of repressing mRNA expression through binding to specific 73 3'UTR target sites [2]. In postembryonic cells, this repressor mechanism mainly acts by 74 destabilizing the mRNA through decapping and poly(A)-tail...

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