Effect of focal ischemia on long noncoding RNAs.

Effect of focal ischemia on long noncoding RNAs.
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DOI:
10.1161/strokeaha.112.669465
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发表时间:
2012-10
期刊:
影响因子:
8.3
通讯作者:
Vemuganti R
Vemuganti R
中科院分区:
医学1区
文献类型:
--
作者:
Dharap A;Nakka VP;Vemuganti R

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长链非编码RNA(lncRNA)在细胞生理学中起着重要作用。我们使用微阵列评估了局灶性缺血对大鼠大脑皮层中8,314个lncRNA表达的影响。短暂性大脑中动脉闭塞诱导缺血。用生物信息学方法对脑卒中应答性lncRNA及其启动子中转录因子结合位点的基因组学和转录组学相关性进行了评估。与假手术相比,MCAO后再灌注3 h至12 h,359个lncRNA上调(>2倍),84个下调(<0.5倍)。62个脑卒中应答性lncRNA与蛋白质编码基因的外显子显示>90%的序列同源性。中风响应lncRNA基因及其同源蛋白编码基因的启动子显示出高度重叠的转录因子结合位点。尽管存在ORF,但lncRNA在体外翻译时不形成任何产物。中风显著改变脑lncRNA表达谱。
Long noncoding RNAs (lncRNAs) play a significant role in cellular physiology. We evaluated the effect of focal ischemia on the expression of 8,314 lncRNAs in rat cerebral cortex using microarrays. Ischemia was induced by transient middle cerebral artery occlusion. Genomic and transcriptomic correlates of the stroke-responsive lncRNAs and the transcription factor binding sties in their promoters were evaluated with bioinformatics. 359 lncRNAs were upregulated (>2-fold) and 84 were downregulated (<0.5 fold) at 3h to 12h of reperfusion following MCAO compared to sham. 62 stroke-responsive lncRNAs showed >90% sequence homology with exons of protein-coding genes. Promoters of stroke-responsive lncRNA genes and their homologous protein-coding genes showed highly overlapping transcription factor binding sites. Despite presence of ORFs, lncRNAs did not form any product when subjected to in vitro translation. Stroke significantly alters cerebral lncRNA expression profiles.