Department of Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE), Von Siebold Str. 3a, 37075, Goettingen, Germany.
Bioinformatics Unit, German Center for Neurodegenerative Diseases (DZNE), Von Siebold Str. 3a, 37075, Goettingen, Germany.
Mol Neurobiol. 2021 Jun;58(6):2940-2953. doi: 10.1007/s12035-021-02296-y. Epub 2021 Feb 10.
Neurons are highly compartmentalized cells that depend on local protein synthesis. Messenger RNAs (mRNAs) have thus been detected in neuronal dendrites, and more recently in the pre- and postsynaptic compartments as well. Other RNA species such as microRNAs have also been described at synapses where they are believed to control mRNA availability for local translation. A combined dataset analyzing the synaptic coding and non-coding RNAome via next-generation sequencing approaches is, however, still lacking. Here, we isolate synaptosomes from the hippocampus of young wild-type mice and provide the coding and non-coding synaptic RNAome. These data are complemented by a novel approach for analyzing the synaptic RNAome from primary hippocampal neurons grown in microfluidic chambers. Our data show that synaptic microRNAs control almost the entire synaptic mRNAome, and we identified several hub microRNAs. By combining the in vivo synaptosomal data with our novel microfluidic chamber system, our findings also support the hypothesis that part of the synaptic microRNAome may be supplied to neurons via astrocytes. Moreover, the microfluidic system is suitable for studying the dynamics of the synaptic RNAome in response to stimulation. In conclusion, our data provide a valuable resource and point to several important targets for further research.
神经元是高度分隔的细胞,依赖于局部蛋白质合成。因此,信使 RNA(mRNA)已在神经元树突中被检测到,最近在突触前和突触后区也被检测到。其他 RNA 种类,如 microRNAs,也在突触处被描述,据信它们可以控制用于局部翻译的 mRNA 的可用性。然而,目前仍然缺乏通过下一代测序方法分析突触编码和非编码 RNA 组的综合数据集。在这里,我们从小鼠海马体中分离出突触体,并提供了编码和非编码的突触 RNA 组。这些数据由一种从在微流控室中生长的原代海马神经元中分析突触 RNA 组的新方法补充。我们的数据表明,突触 microRNAs 几乎控制整个突触 mRNA 组,并且我们鉴定了几个枢纽 microRNAs。通过将体内突触体数据与我们的新型微流控室系统相结合,我们的发现还支持部分突触 microRNA 组可能通过星形胶质细胞供应给神经元的假设。此外,该微流控系统适合研究刺激对突触 RNA 组动态的影响。总之,我们的数据提供了有价值的资源,并指出了几个进一步研究的重要目标。