Effect of (S)-3,5-DHPG on microRNA expression in mouse brain
Effect of (S)-3,5-DHPG on microRNA expression in mouse brain
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DOI：
10.1016/j.expneurol.2012.01.018
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发表时间：
2012-06-01
影响因子：
5.3
通讯作者：
Saugstad, Julie A.
中科院分区：
文献类型：
--
作者：
Lusardi, Theresa A.;Thompson, Simon J.;Saugstad, Julie A.
MicroRNA是一类调控转录后基因表达的小分子非编码RNA。在发现microRNA后的短时间内，文献已经蓬勃发展，研究集中在microRNA的生物合成，靶点预测和结合，以及microRNA的翻译抑制机制。鉴于microRNA在细胞生物学的所有领域中的突出作用，microRNA也与人类疾病（包括神经系统疾病）有关也就不足为奇了。microRNA研究中研究最少的领域之一是它们的表达在发育和癌症之外是如何调节的。因此，我们研究了小鼠脑中神经递质受体激活对microRNA的调节作用。本研究采用侧脑室注射选择性激动剂（S）-3，5-二羟基苯甘氨酸（DHPG）的方法，对小鼠脑I组代谢型谷氨酸受体进行了研究。然后，我们在注射DHPG后4、8和24 h通过Ambion和Invitrogen微阵列检测大脑皮层中microRNA的表达，并通过SABiosciences qPCR阵列检测成熟microRNA序列的表达。这些研究表明，在微阵列和qPCR阵列中，DHPG注射后8小时检测到最大数量的显著调节的microRNA。然后，我们使用RNA印迹定量microRNA表达，并在原位杂交检查由DHPG调节的microRNA的细胞分布。在所有三个阵列中DHPG后8小时调节的microRNA的生物信息学分析揭示了已知与I组mGluR效应相关的KEGG途径，以及最近描述的新途径。这些研究首次表明DHGP调节小鼠大脑皮层中microRNA的表达，并支持I组mGluRs可能调节小鼠大脑中microRNA表达的假设。(c)2012 Elsevier Inc. All rights reserved.
MicroRNAs are small non-coding RNAs that regulate post-transcriptional gene expression. In the short time since the discovery of microRNAs, the literature has burgeoned with studies focused on the biosynthesis of microRNAs, target prediction and binding, and mechanisms of translational repression by microRNAs. Given the prominent role of microRNAs in all areas of cell biology, it is not surprising that microRNAs are also linked to human diseases, including those of the nervous system. One of the least-studied areas of microRNA research is how their expression is regulated outside of development and cancer. Thus, we examined a role for regulation of microRNAs by neurotransmitter receptor activation in mouse brain. We focused on the group I metabotropic glutamate receptors by using intracerebroventricular injection of the selective agonist, (S)-3,5-dihydroxyphenylglycine (DHPG) in mouse brain. We then examined the expression of microRNAs in the cerebral cortex by Ambion and Invitrogen microarrays, and the expression of mature microRNA sequences by SABiosciences qPCR arrays, at 4, 8 and 24 h after DHPG injection. These studies revealed that the largest number of significantly regulated microRNAs was detected 8 h after DHPG injection in the microarrays and qPCR arrays. We then used RNA blots to quantify microRNA expression, and in situ hybridization to examine cellular distribution of the microRNAs regulated by DHPG. Bioinformatic analysis of the microRNAs regulated 8 h after DHPG in all three arrays revealed KEGG pathways that are known to correlate with group I mGluR effects, as well as recently described and novel pathways. These studies are the first to show that DHGP regulates the expression of microRNAs in mouse cerebral cortex, and support the hypothesis that group I mGluRs may regulate microRNA expression in mouse brain. (c) 2012 Elsevier Inc. All rights reserved.