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A Complex Network of MicroRNAs Expressed in Brain and Genes Associated with Amyotrophic Lateral Sclerosis

机译:在大脑和肌萎缩性侧索硬化相关基因中表达的MicroRNA的复杂网络。

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Amyotrophic Lateral Sclerosis (ALS) is a rare neurological disease affecting mainly motor neurons and often leads to paralysis and death in extreme cases. For exploring the role of microRNAs in genes regulation in ALS disease, miRanda was employed for prediction of target sites of miRNAs expressed in various parts of brain and CNS on 35 genes associated with ALS. Similar search was conducted using TargetScan and PicTar for prediction of target sites in 3' UTR only. 1456 target sites were predicted using miRanda and more target sites were found in 5' UTR and CDS region as compared to 3' UTR. 11 target sites were predicted to be common by all the algorithms and, thus, these represent the most significant sites. Target site hotspots were identified and were recognized as hotspots for multiple miRNAs action, thus, acting as favoured sites of action for the repression of gene expression. The complex interplay of genes and miRNAs brought about by multiplicity and cooperativity was explored. This investigation will aid in elucidating the mechanism of action of miRNAs for the considered genes. The intrinsic network of miRNAs expressed in nervous system and genes associated with ALS may provide rapid and effective outcome for therapeutic applications and diagnosis.
机译:肌萎缩性侧索硬化症(ALS)是一种罕见的神经系统疾病,主要影响运动神经元,在极端情况下经常导致瘫痪和死亡。为了探索microRNA在ALS疾病的基因调控中的作用,采用miRanda预测了在与ALS相关的35个基因上大脑和CNS各个部位表达的miRNA的靶位。使用TargetScan和PicTar进行了类似的搜索,仅预测3'UTR中的目标位点。使用miRanda预测了1456个目标位点,与3'UTR相比,在5'UTR和CDS区域发现了更多的目标位点。所有算法都预测有11个目标站点是共同的,因此,这些站点是最重要的站点。鉴定出靶位点热点,并将其识别为多种miRNA作用的热点,因此,成为抑制基因表达的有利作用位点。探索了由多重性和协同性带来的基因和miRNA的复杂相互作用。这项研究将有助于阐明miRNA对所考虑基因的作用机制。在神经系统中表达的miRNA固有网络以及与ALS相关的基因可能为治疗应用和诊断提供快速有效的结果。

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