vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJ20.613vavilov-2550Research ArticleГЕНЕТИКА ЧЕЛОВЕКАHUMAN GENETICSУчастие мобильных элементов в нейрогенезеInvolvement of transposable elements in neurogenesishttps://orcid.org/0000-0002-4091-382XМустафинР. Н.MustafinR. N.ruji79@mail.ruhttps://orcid.org/0000-0003-2987-3334ХуснутдиноваЭ. К.KhusnutdinovaE. K.Башкирский государственный медицинский университетРоссияBashkir State Medical UniversityRussian FederationИнститут биохимии и генетики – обособленное структурное подразделение Уфимского федерального исследовательского центра Российской академии наукРоссияInstitute of Biochemistry and Genetics – Subdivision of the Ufa Federal Research Centre of the Russian Academy of SciencesRussian Federation202024042020242209218Copyright © Мустафин Р.Н., Хуснутдинова Э.К., 20202020Мустафин Р.Н., Хуснутдинова Э.К.Mustafin R.N., Khusnutdinova E.K.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/2550

В обзоре представлены накопленные в научной литературе данные об участии мобильных генетических элементов в регуляции дифференцировки нейрональных стволовых клеток и функционирования зрелых нейронов головного мозга. Начиная с первого деления зиготы, эмбриональное развитие управляется закономерными активациями транспозонов, необходимыми для последовательного изменения экспрессии специфических для каждого типа клеток генов. Частным отражением этих процессов может быть дифференцировка нейрональных стволовых клеток – процесс, в ходе которого необходима наиболее тонкая настройка экспрессии генов в нейронах различных областей головного мозга. Доказательствами этого предположения являются данные о высокой активности транспозонов в центре нейро-генеза, зубчатой извилине гиппокампа. Кроме того, мобильные элементы – источники возникновения и эволюции длинных некодирующих РНК, которые коэкспрессируются с необходимыми для работы головного мозга белок-кодирующими генами. Наибольшая активность длинных некодирующих РНК, так же как и транспозонов, обнаружена в центре нейрогенеза человека, что позволяет предположить их участие в управлении работой головного мозга. В регуляции дифференцировкой нейрональных стволовых клеток используются также микроРНК, многие из которых возникают из транскриптов мобильных элементов.  Транспозоны посредством собственных процессированных транскриптов играют роль в эпигенетической регуляции дифференцировки нейронов. Объяснением глобальной регуляторной функции мобильных элементов в головном мозге человека может служить их значение в возникновении белок-кодирующих генов в эволюции путем экзонизации, дупликации и доместикации. Эти гены вовлечены в эпигенетическую регуляторную сеть с участием транспозонов, так как содержат нуклеотидные последовательности, комплементарные микроРНК и длинным некодирующим РНК, образуемым из транскриптов мобильных элементов.  В формировании памяти выявлена роль обмена вирусоподобными частицами мРНК при помощи белка Arc эндогенных ретровирусов HERV между нейронами. Возможными способами реализации этого механизма могут быть обратная транскрипция мРНК и сайт-специфическая интеграция в геном с регуляторным воздействием на гены, участвующие в консолидации информации.  

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 mosai cism 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.  

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The authors declare that there are no conflicts of interest present.