新型mirna与编码序列和非翻译区具有三核苷酸重复序列的mRNA候选基因相互作用的特点

A. Belkozhayev, R. Niyazova, C. Wilson
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引用次数: 0

摘要

三核苷酸重复疾病是一组主要由重复序列扩增引起的遗传性神经系统疾病。mirna在转录调控中发挥重要作用,并在中枢神经系统中选择性地大量表达。在本研究中,MirTarget程序预测了具有三核苷酸重复序列的基因的mrna中的mirna结合位点。MirTarget程序决定了以下结合特征:开始启动miRNA与mrna的结合;miRNA结合位点在5'UTRs、cds和3'UTRs的定位;自由结合能;以及mirna和mrna之间的核苷酸相互作用方案。编码序列中,ID00372.5p-miR与具有CAG (Q)重复序列的ATXN2、FMN2和MN1基因mRNA的结合位点显示出最高的自由结合能。ADRBK1、BRSK2、C11orf87和FMR1基因的mRNA在5'UTR具有CGG重复区的ID01508.5p-miR结合位点。BLMH基因5'UTR中ID00296.3p-miR和ID01702.3p-miR的结合位点与CCG重复序列相互作用。具有CUG重复区的DMPK基因在3'UTR中有ID00522.5p-miR结合位点。基于这些结果,ID00372.5p-miR、ID01508.5p-miR、id00296.5 p- mir、ID01702.3p-miR和ID00522.5pmiR及其靶基因ATXN2、FMN2、MN1、ADRBK1、BRSK2、C11orf87、FMR1、BLMH和DMPK的相互作用可用于开发神经系统疾病的诊断和治疗靶点方法。
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The features of novel miRNAs interaction with mRNA candidate genes having trinucleotide repeats in coding sequences and untranslated regions
Trinucleotide repeat disorders are a group of predominantly inherited neurological diseases caused by the expansion of repetitive sequences. miRNAs play major roles in transcriptional regulation and are expressed selectively and abundantly in the central nervous system. In the present research, MirTarget program predicted the miRNA-binding sites in mRNAs of genes with trinucleotide repeats. The MirTarget programme determines the following features of binding: the start of the initiation of miRNA binding to mRNAs; the localization of miRNA binding sites in 5’UTRs, CDSs and 3’UTRs; the free energy of binding; and the schemes of nucleotide interactions between miRNAs and mRNAs. In coding sequences the binding sites of ID00372.5p-miR with mRNA of ATXN2, FMN2 and MN1 genes having CAG (Q) repeats show the highest free binding energy. The mRNA of ADRBK1, BRSK2, C11orf87 and FMR1 genes have ID01508.5p-miR binding sites in 5’UTR with CGG repeated regions. Also, the binding sites of ID00296.3p-miR and ID01702.3p-miR in 5’UTR of BLMH gene interacted with CCG repeats. DMPK gene with CUG repeated regions have ID00522.5p-miR binding sites in 3’UTR. Based on these results, the interactions of ID00372.5p-miR, ID01508.5p-miR, ID00296.3p-miR, ID01702.3p-miR and ID00522.5pmiR and their target genes ATXN2, FMN2, MN1, ADRBK1, BRSK2, C11orf87, FMR1, BLMH and DMPK can be used for developing methods for diagnosing and therapeutic targets for neurological disorders.
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