Zhong Jun, Chuang Shih-Chieh, Bianchi Riccardo, Zhao Wangfa, Lee Heekyung, Fenton André A, Wong Robert K S, Tiedge Henri
The Robert F. Furchgott Center for Neural and Behavioral Science, Department of Physiology and Pharmacology, State University of New York, Brooklyn, 11203, USA.
J Neurosci. 2009 Aug 12;29(32):9977-86. doi: 10.1523/JNEUROSCI.3893-08.2009.
Regulatory RNAs have been suggested to contribute to the control of gene expression in eukaryotes. Brain cytoplasmic (BC) RNAs are regulatory RNAs that control translation initiation. We now report that neuronal BC1 RNA plays an instrumental role in the protein-synthesis-dependent implementation of neuronal excitation-repression equilibria. BC1 repression counter-regulates translational stimulation resulting from synaptic activation of group I metabotropic glutamate receptors (mGluRs). Absence of BC1 RNA precipitates plasticity dysregulation in the form of neuronal hyperexcitability, elicited by group I mGluR-stimulated translation and signaled through the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathway. Dysregulation of group I mGluR function in the absence of BC1 RNA gives rise to abnormal brain function. Cortical EEG recordings from freely moving BC1(-/-) animals show that group I mGluR-mediated oscillations in the gamma frequency range are significantly elevated. When subjected to sensory stimulation, these animals display an acute group I mGluR-dependent propensity for convulsive seizures. Inadequate RNA control in neurons is thus causally linked to heightened group I mGluR-stimulated translation, neuronal hyperexcitability, heightened gamma band oscillations, and epileptogenesis. These data highlight the significance of small RNA control in neuronal plasticity.
调控性RNA被认为有助于真核生物中基因表达的控制。脑细胞质（BC）RNA是控制翻译起始的调控性RNA。我们现在报告，神经元BC1 RNA在神经元兴奋-抑制平衡的蛋白质合成依赖性实现中发挥着重要作用。BC1的抑制作用对I组代谢型谷氨酸受体（mGluRs）突触激活所导致的翻译刺激起到反调节作用。BC1 RNA的缺失会以神经元过度兴奋的形式引发可塑性失调，这种过度兴奋由I组mGluR刺激的翻译引发，并通过丝裂原活化蛋白激酶激酶/细胞外信号调节激酶途径传导信号。在没有BC1 RNA的情况下，I组mGluR功能失调会导致脑功能异常。对自由活动的BC1（-/-）动物进行的皮质脑电图记录显示，I组mGluR介导的γ频率范围内的振荡显著增强。当受到感觉刺激时，这些动物表现出急性的I组mGluR依赖性惊厥发作倾向。因此，神经元中RNA控制不足与I组mGluR刺激的翻译增强、神经元过度兴奋、γ波段振荡增强以及癫痫发生存在因果关系。这些数据突出了小RNA控制在神经元可塑性中的重要性。
