Bicker Silvia, Lackinger Martin, Weiß Kerstin, Schratt Gerhard
Biochemical-Pharmacological Center (BPC) Marburg, Institute of Physiological Chemistry, Philipps-University Marburg, Marburg, Germany.
Cell Mol Life Sci. 2014 Oct;71(20):3987-4005. doi: 10.1007/s00018-014-1671-7. Epub 2014 Jul 10.
Dendritic mRNA transport and local translation in the postsynaptic compartment play an important role in synaptic plasticity, learning and memory. Local protein synthesis at the synapse has to be precisely orchestrated by a plethora of factors including RNA binding proteins as well as microRNAs, an extensive class of small non-coding RNAs. By binding to complementary sequences in target mRNAs, microRNAs fine-tune protein synthesis and thereby represent critical regulators of gene expression at the post-transcriptional level. Research over the last years identified an entire network of dendritic microRNAs that fulfills an essential role in synapse development and physiology. Recent studies provide evidence that these small regulatory molecules are highly regulated themselves, at the level of expression as well as function. The importance of microRNAs for correct function of the nervous system is reflected by an increasing number of studies linking dysregulation of microRNA pathways to neurological disorders. By focusing on three extensively studied examples (miR-132, miR-134, miR-138), this review will attempt to illustrate the complex regulatory roles of dendritic microRNAs at the synapse and their implications for pathological conditions.
树突状mRNA运输和突触后区室中的局部翻译在突触可塑性、学习和记忆中发挥着重要作用。突触处的局部蛋白质合成必须由大量因素精确协调,这些因素包括RNA结合蛋白以及微小RNA(一类广泛的小型非编码RNA)。通过与靶mRNA中的互补序列结合,微小RNA对蛋白质合成进行微调,从而在转录后水平上代表基因表达的关键调节因子。过去几年的研究确定了一个完整的树突状微小RNA网络,该网络在突触发育和生理学中发挥着重要作用。最近的研究提供了证据,表明这些小调节分子自身在表达水平和功能水平上都受到高度调控。越来越多的研究将微小RNA通路的失调与神经系统疾病联系起来,这反映了微小RNA对神经系统正常功能的重要性。通过聚焦三个经过广泛研究的例子(miR-132、miR-134、miR-138),本综述将试图阐明树突状微小RNA在突触处的复杂调节作用及其对病理状况的影响。