Mustafin R N, Khusnutdinova E K
Bashkir State Medical University, Ufa, Russia.
Institute of Biochemistry and Genetics - Subdivision of the Ufa Federal Research Centre of the Russian Academy of Sciences, Ufa, Russia.
Vavilovskii Zhurnal Genet Selektsii. 2020 Mar;24(2):209-218. doi: 10.18699/VJ20.613.
The article is about the role of transposons in the regulation of functioning of neuronal stem cells and mature neurons of the human brain. Starting from the first division of the zygote, embryonic development is governed by regular activations of transposable elements, which are necessary for the sequential regulation of the expression of genes specific for each cell type. These processes include differentiation of neuronal stem cells, which requires the finest tuning of expression of neuron genes in various regions of the brain. Therefore, in the hippocampus, the center of human neurogenesis, the highest transposon activity has been identified, which causes somatic mosaicism of cells during the formation of specific brain structures. Similar data were obtained in studies on experimental animals. Mobile genetic elements are the most important sources of long non-coding RNAs that are coexpressed with important brain protein-coding genes. Significant activity of long non-coding RNA was detected in the hippocampus, which confirms the role of transposons in the regulation of brain function. MicroRNAs, many of which arise from transposon transcripts, also play an important role in regulating the differentiation of neuronal stem cells. Therefore, transposons, through their own processed transcripts, take an active part in the epigenetic regulation of differentiation of neurons. The global regulatory role of transposons in the human brain is due to the emergence of protein-coding genes in evolution by their exonization, duplication and domestication. These genes are involved in an epigenetic regulatory network with the participation of transposons, since they contain nucleotide sequences complementary to miRNA and long non-coding RNA formed from transposons. In the memory formation, the role of the exchange of virus-like mRNA with the help of the Arc protein of endogenous retroviruses HERV between neurons has been revealed. A possible mechanism for the implementation of this mechanism may be reverse transcription of mRNA and site-specific insertion into the genome with a regulatory effect on the genes involved in the memory.
这篇文章是关于转座子在人类大脑神经元干细胞和成熟神经元功能调节中的作用。从受精卵的第一次分裂开始，胚胎发育受转座元件的定期激活控制，这对于每种细胞类型特异性基因表达的顺序调节是必需的。这些过程包括神经元干细胞的分化，这需要对大脑各个区域的神经元基因表达进行精细调节。因此，在人类神经发生的中心海马体中，已发现最高的转座子活性，这在特定脑结构形成过程中导致细胞的体细胞镶嵌现象。在对实验动物的研究中也获得了类似的数据。移动遗传元件是与重要脑蛋白编码基因共表达的长链非编码RNA的最重要来源。在海马体中检测到长链非编码RNA的显著活性，这证实了转座子在脑功能调节中的作用。许多微小RNA源自转座子转录本，它们在调节神经元干细胞的分化中也起着重要作用。因此，转座子通过其自身加工的转录本，积极参与神经元分化的表观遗传调节。转座子在人类大脑中的全局调节作用归因于其在进化过程中通过外显子化、复制和驯化产生蛋白质编码基因。这些基因参与了一个有转座子参与的表观遗传调控网络，因为它们包含与由转座子形成的微小RNA和长链非编码RNA互补的核苷酸序列。在记忆形成过程中，已经揭示了内源性逆转录病毒HERV的Arc蛋白在神经元之间帮助病毒样mRNA交换的作用。这种机制实现的一种可能机制可能是mRNA的逆转录和位点特异性插入基因组，对参与记忆的基因产生调节作用。
