Prediction of altered 3'- UTR miRNA-binding sites from RNA-Seq data: the swine leukocyte antigen complex (SLA) as a model region.
Prediction of altered 3'- UTR miRNA-binding sites from RNA-Seq data: the swine leukocyte antigen complex (SLA) as a model region.
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DOI：
10.1371/journal.pone.0048607
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Giuffra E
中科院分区：
文献类型：
--
作者：
Endale Ahanda ML;Fritz ER;Estellé J;Hu ZL;Madsen O;Groenen MA;Beraldi D;Kapetanovic R;Hume DA;Rowland RR;Lunney JK;Rogel-Gaillard C;Reecy JM;Giuffra E
SLA（猪白细胞抗原，MHC：SLA）基因是猪免疫、传染病和疫苗应答的最重要的决定因素;已经报道了与免疫和猪生产性状的几种遗传关联。然而，目前关于SLA的大部分知识仅限于基因编码区。微小RNA（microRNAs，miRNAs）是一类转录后调节后生动物大量蛋白质编码基因表达的小分子，在调节免疫机制和疾病反应中发挥重要作用。miRNA或其基因靶点的多态性可能通过消除、削弱或创建miRNA靶位点对基因表达产生显著影响，可能导致表型变异。我们探索了整个SLA区域内基因的3′-UTR miRNA靶位点变异的影响。TargetScan、PACMIT和TargetSpy基于不同生物学参数的组合预测使得能够识别miRNA靶位点和发现多态性miRNA靶位点（poly-miRTSs）。对特征在于不同序列变异范围的三个SLA基因的预测提供了从收集自不同猪组织的总共144 M RNA-Seq读数分析poly-miRTSs的原理证明。预测24个新的SNP影响SLA区域的19个基因中的miRNA结合位点。这些基因中的七个（SLA-1、SLA-6、SLA-DQA、SLA-DQB 1、SLA-DOA、SLA-DOB和TAP 1）与抗原加工和呈递功能相关，这让人想起与人类中改变的与MHC基因结合的miRNA所报告的疾病性状的关联。通过利用三种猪组织的公开数据集（RNA-Seq和小RNA-Seq），证明了miRNA和共表达的SLA靶标之间的表达水平的负相关性。我们的研究结果支持RNA-Seq集合的资源价值，以识别可能导致改变miRNA调控模式的SNP。
The SLA (swine leukocyte antigen, MHC: SLA) genes are the most important determinants of immune, infectious disease and vaccine response in pigs; several genetic associations with immunity and swine production traits have been reported. However, most of the current knowledge on SLA is limited to gene coding regions. MicroRNAs (miRNAs) are small molecules that post-transcriptionally regulate the expression of a large number of protein-coding genes in metazoans, and are suggested to play important roles in fine-tuning immune mechanisms and disease responses. Polymorphisms in either miRNAs or their gene targets may have a significant impact on gene expression by abolishing, weakening or creating miRNA target sites, possibly leading to phenotypic variation. We explored the impact of variants in the 3′-UTR miRNA target sites of genes within the whole SLA region. The combined predictions by TargetScan, PACMIT and TargetSpy, based on different biological parameters, empowered the identification of miRNA target sites and the discovery of polymorphic miRNA target sites (poly-miRTSs). Predictions for three SLA genes characterized by a different range of sequence variation provided proof of principle for the analysis of poly-miRTSs from a total of 144 M RNA-Seq reads collected from different porcine tissues. Twenty-four novel SNPs were predicted to affect miRNA-binding sites in 19 genes of the SLA region. Seven of these genes (SLA-1, SLA-6, SLA-DQA, SLA-DQB1, SLA-DOA, SLA-DOB and TAP1) are linked to antigen processing and presentation functions, which is reminiscent of associations with disease traits reported for altered miRNA binding to MHC genes in humans. An inverse correlation in expression levels was demonstrated between miRNAs and co-expressed SLA targets by exploiting a published dataset (RNA-Seq and small RNA-Seq) of three porcine tissues. Our results support the resource value of RNA-Seq collections to identify SNPs that may lead to altered miRNA regulation patterns.
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影响因子：
4.4
作者：
Chen C;Ai H;Ren J;Li W;Li P;Qiao R;Ouyang J;Yang M;Ma J;Huang L
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影响因子：
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作者：
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通讯作者：
Hofacker, Ivo L.
影响因子：
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作者：
Gaidatzis D;van Nimwegen E;Hausser J;Zavolan M
通讯作者：
Zavolan M
影响因子：
3.7
作者：
Derrien T;Estellé J;Marco Sola S;Knowles DG;Raineri E;Guigó R;Ribeca P
通讯作者：
Ribeca P
影响因子：
64.8
作者：
Kulkarni, Smita;Savan, Ram;Qi, Ying;Gao, Xiaojiang;Yuki, Yuko;Bass, Sara E.;Martin, Maureen P.;Hunt, Peter;Deeks, Steven G.;Telenti, Amalio;Pereyra, Florencia;Goldstein, David;Wolinsky, Steven;Walker, Bruce;Young, Howard A.;Carrington, Mary
通讯作者：
Carrington, Mary