与微小RNA结合位点多态性相关的基因表达改变

Altered Gene Expression Associated with microRNA Binding Site Polymorphisms.

作者信息

Võsa Urmo, Esko Tõnu, Kasela Silva, Annilo Tarmo

机构信息

Estonian Genome Center, University of Tartu, Riia 23b, 51010 Tartu, Estonia.

Estonian Genome Center, University of Tartu, Riia 23b, 51010 Tartu, Estonia; Division of Endocrinology, Children's Hospital, Boston, MA, United States of America; Department of Genetics, Harvard Medical School, Boston, MA, United States of America; Broad Institute, Cambridge, MA, United States of America.

出版信息

PLoS One. 2015 Oct 23;10(10):e0141351. doi: 10.1371/journal.pone.0141351. eCollection 2015.

Abstract

Allele-specific gene expression associated with genetic variation in regulatory regions can play an important role in the development of complex traits. We hypothesized that polymorphisms in microRNA (miRNA) response elements (MRE-SNPs) that either disrupt a miRNA binding site or create a new miRNA binding site can affect the allele-specific expression of target genes. By integrating public expression quantitative trait locus (eQTL) data, miRNA binding site predictions, small RNA sequencing, and Argonaute crosslinking immunoprecipitation (AGO-CLIP) datasets, we identified genetic variants that can affect gene expression by modulating miRNA binding efficiency. We also identified MRE-SNPs located in regions associated with complex traits, indicating possible causative mechanisms associated with these loci. The results of this study expand the current understanding of gene expression regulation and help to interpret the mechanisms underlying eQTL effects.

摘要

与调控区域遗传变异相关的等位基因特异性基因表达在复杂性状的发展中可能起重要作用。我们假设,微小RNA(miRNA)反应元件(MRE - SNP)中的多态性,即破坏miRNA结合位点或创建新的miRNA结合位点,可影响靶基因的等位基因特异性表达。通过整合公共表达定量性状位点(eQTL)数据、miRNA结合位点预测、小RNA测序和AGO蛋白交联免疫沉淀(AGO - CLIP)数据集,我们鉴定出了可通过调节miRNA结合效率来影响基因表达的遗传变异。我们还鉴定出位于与复杂性状相关区域的MRE - SNP,这表明了与这些位点相关的可能致病机制。本研究结果扩展了目前对基因表达调控的理解,并有助于解释eQTL效应背后的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de9e/4619707/6093e15e7ba8/pone.0141351.g001.jpg

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