Climbing fibers induce microRNA transcription in cerebellar Purkinje cells.
Climbing fibers induce microRNA transcription in cerebellar Purkinje cells.
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DOI：
10.1016/j.neuroscience.2010.09.039
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发表时间：
2010-12-15
期刊：
影响因子：
3.3
通讯作者：
Yakhnitsa, V.
中科院分区：
文献类型：
--
作者：
Barmack, N. H.;Qian, Z.;Yakhnitsa, V.
为了维持突触传递的简单变化，可能需要多达100种蛋白质的协调表达。虽然每种蛋白质可能被单独调节，但多种蛋白质的翻译可能被microrna调节。MicroRNAs是一种短的非编码rna，可在翻译上抑制靶mrna中的同源序列。如果这些目标序列在多个基因中共享，那么单个microRNA就可以有效地并行调节多个基因的活性。在这里，我们研究了小鼠小脑小叶攀爬纤维-浦肯野细胞突触的自然诱发突触活动是否影响microRNA转录。小鼠接受24小时的双眼水平光动力刺激（HOKS），可引起一只小叶对浦肯野细胞的攀爬纤维活性持续增加，而另一只小叶对浦肯野细胞的攀爬纤维活性持续降低。攀爬纤维活性的增加增加了小叶中12种microrna的转录。其中一种microrna miR335的转录与刺激时间成正比，在HOKS 24小时后增加了18倍。我们使用杂交组织化学将miR335转录物定位到浦肯野细胞。在HOKS停止后3小时内，miR335转录本衰减到基线水平。我们使用多种筛选方法确定miR335的mRNA靶点：序列分析、miR335抑制剂的显微注射和鉴定在HOKS期间转录减少的mRNA。两个基因，calbindin和14-3-3-θ通过了这些筛选。我们的数据表明，microRNA转录可能为调节浦肯野细胞可塑性的蛋白质提供重要的突触或稳态机制。
The coordinated expression of as many as 100 proteins may be required to sustain simple changes in synaptic transmission. While each protein may be regulated separately, the translation of multiple proteins could be regulated by microRNAs. MicroRNAs are short non coding RNAs that translationally repress cognate sequences in targeted mRNAs. If these targeted sequences are shared across several genes, then a single microRNA could, effectively regulate the activity of several genes in parallel. Here we investigate whether microRNA transcription is influenced by naturally evoked synaptic activity at the climbing fiber-Purkinje cell synapse in the mouse cerebellar flocculus. Mice received 24 h of binocular horizontal optokinetic stimulation (HOKS) evoking sustained increases in climbing fiber activity to Purkinje cells in one flocculus and decreases to Purkinje cells in the other. Increased climbing fiber activity increased transcription of twelve microRNAs in the flocculus. The transcription of one of these microRNAs, miR335, was proportional to duration of stimulation, increasing 18-fold after 24 h of HOKS. We localized miR335 transcripts to Purkinje cells using hybridization histochemistry. Transcripts of miR335 decayed to baseline within 3 h after HOKS was stopped. We identified mRNA targets for miR335 using multiple screens: sequence analysis, microinjection of miR335 inhibitors and identification of mRNAs whose transcription decreased during HOKS. Two genes, calbindin and 14-3-3-θ passed these screens. Our data suggest that microRNA transcription could provide an important synaptic or homeostatic mechanism for the regulation of proteins that contribute to Purkinje cell plasticity.
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