Transient focal ischemia induces extensive temporal changes in rat cerebral microRNAome.
Transient focal ischemia induces extensive temporal changes in rat cerebral microRNAome.
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DOI：
10.1038/jcbfm.2008.157
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发表时间：
2009-04
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影响因子：
--
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MicroRNAs(MiRNAs)是一种长约22个核苷酸的非编码RNA，通过降解mRNAs或阻止其翻译来控制细胞功能。为了了解它们在缺血病理生理学中的功能意义，我们描述了成年大鼠大脑中miRNAs在短暂性大脑中动脉闭塞后再灌注时间的变化。与假手术组相比，238个miRNAs在3h至3d的5个再灌流时间点中，至少有4个表达增加，12个表达降低。其中，17个出现了5倍的变化。生物信息学分析表明，miRNAs改变为几个已知的介导炎症、转录、神经保护、受体功能和离子稳态的mRNAs之间存在相关性。Antag omir介导的对mir-145表达的抑制导致其下游靶标超氧化物歧化酶-2在缺血后脑组织中的蛋白表达增加。计算机分析显示，局灶性脑缺血后诱导的8个miRNAs与877个启动子具有序列互补性，表明非编码RNA可能诱导了基因表达的激活。短暂性大脑中动脉闭塞后，调节miRNA生物合成的核糖核酸酶DROSHA和DICER、辅因子PashA和前miRNA转运体exportin-5的mRNA表达没有改变。因此，目前的研究表明miRNAs在脑缺血后控制mRNA转录和翻译中起着关键作用。
MicroRNAs (miRNAs) are ~22 nucleotides long, noncoding RNAs that control cellular function by either degrading mRNAs or arresting their translation. To understand their functional significance in ischemic pathophysiology, we profiled miRNAs in adult rat brain as a function of reperfusion time after transient middle cerebral artery occlusion. Of the 238 miRNAs evaluated, 8 showed increased and 12 showed decreased expression at least at 4 out of 5 reperfusion time points studied between 3 h and 3 days compared with sham. Of those, 17 showed >5 fold change. Bioinformatics analysis indicated a correlation between miRNAs altered to several mRNAs known to mediate inflammation, transcription, neuroprotection, receptors function, and ionic homeostasis. Antagomir-mediated prevention of mir-145 expression led to an increased protein expression of its downstream target superoxide dismutase-2 in the postischemic brain. In silico analysis showed sequence complementarity of eight miRNAs induced after focal ischemia to 877 promoters indicating the possibility of noncoding RNA-induced activation of gene expression. The mRNA expression of the RNases Drosha and Dicer, cofactor Pasha, and the pre-miRNA transporter exportin-5, which modulate miRNA biogenesis, were not altered after transient middle cerebral artery occlusion. Thus, the present studies indicate a critical role of miRNAs in controlling mRNA transcription and translation in the postischemic brain.
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影响因子：
5.2
作者：
Krichevsky, Anna M.;Sonntag, Kai-C.;Kosik, Kenneth S.
通讯作者：
Kosik, Kenneth S.
DOI：
10.1073/pnas.0710263105
发表时间：
2008-04-29
影响因子：
11.1
作者：
Hebert, Sebastien S.;Horre, Katrien;De Strooper, Bart
通讯作者：
De Strooper, Bart
DOI：
10.1073/pnas.0707594105
发表时间：
2008-02-05
影响因子：
11.1
作者：
Place, Robert F.;Li, Long-Cheng;Dahiya, Rajvir
通讯作者：
Dahiya, Rajvir
影响因子：
64.5
作者：
Lewis, BP;Shih, IH;Burge, CB
通讯作者：
Burge, CB
DOI：
10.1073/pnas.0506482102
发表时间：
2005-11-22
影响因子：
11.1
作者：
Humphreys, DT;Westman, BJ;Preiss, T
通讯作者：
Preiss, T