psychiatryПСИХИАТРИЯPsychiatry (Moscow) (Psikhiatriya)1683-83192618-6667FSBSI “The Mental Health Research Centre”; LLC «Publisher «MIA»psychiatry-341Research ArticleНАУЧНЫЕ ОБЗОРЫSCIENTIFIC REVIEWSО возможной роли копийности рибосомных генов в развитии психических заболеванийThe possible role of copy number of ribosomal genes in the development of mental disordersПороховникЛ. Н.PorokhovnikL. N.

Пороховник Лев Николаевич - кандидат биологических наук, лаборатория молекулярной биологии, МГНЦ ФАНО.

Москва.

Porokhovnik Lev N. - candidate of biological sciences, laboratory of molecular biology.

Moscow.

med-gen@mail.ruВейкоН. Н.VeikoN. N.

Вейко Наталья Николаевна - доктор биологических наук, лаборатория молекулярной биологии, МГНЦ ФАНО.

Москва.

Veiko Nataliya N. - docteur es sciences, laboratory of molecular biology.

Moscow.

satelit32006@yandex.ruЕршоваЕ. С.ErshovaE. S.

Ершова Елизавета Сергеевна - кандидат биологических наук, научный сотрудник, лаборатория молекулярной биологии, МГНЦ ФАНО.

Москва.

Ershova Elisaveta S. - candidate of biological sciences, laboratory of molecular biology.

Moscow.

es-ershova@rambler.ruКостюкГ. П.KostyukG. P.

Костюк Георгий Петрович - доктор медицинских наук, профессор главный врач, ГБУЗ «ПКБ № 1 им. Н.А. Алексеева».

Москва.

Kostyuk Georgy P. - PhD, MD, professor, Head of Psychiatric Clinical Hospital № 1 name after N.A. Alekseev.

Moscow.

pkbl@zdrav.mos.ruЗахароваН. В.ZakharovaN. V.

Захарова Наталья Вячеславовна - кандидат медицинских наук, ГБУЗ «ПКБ № 1 им. Н.А. Алексеева».

Москва.

Zakharova Nataliya V. - candidate of medical sciences.

Moscow.

nataliza80@gmail.comГорбачевскаяН. Л.GorbachevskayaN. L.

Горбачевская Наталья Леонидовна -  доктор биологических наук, профессор, лаборатория нейрофизиологии, ФГБНУ НЦПЗ.

Москва.

Gorbachevskaya Nataliya L. - docteur es sciences, professor, laboratory of neurophysiology.

Moscow.

gorbachevskaya@yandex.ruКостюкС. В.KostyukS. V.

Костюк Светлана Викторовна - доктор биологических наук, лаборатория молекулярной биологии, МГНЦ ФАНО.

Москва.

Kostyuk Svetlana V. - docteur es sciences, laboratory of molecular biology

Moscow.

svet-vk@yandex.ruФГБНУ «Медико-генетический научный центр»РоссияFSBSI «Research Centre for Medical Genetics»Russian FederationГБУЗ «ПКБ № 1 им. Н.А. Алексеева»РоссияPsychiatric Clinical Hospital № 1 named after N.A. AlekseevRussian FederationФГБНУ «Научный центр психического здоровья»РоссияFSBSI «Mental Health Research Centre»Russian Federation20181311201807889105Copyright © Пороховник Л.Н., Вейко Н.Н., Ершова Е.С., Костюк Г.П., Захарова Н.В., Горбачевская Н.Л., Костюк С.В., 20182018Пороховник Л.Н., Вейко Н.Н., Ершова Е.С., Костюк Г.П., Захарова Н.В., Горбачевская Н.Л., Костюк С.В.Porokhovnik L.N., Veiko N.N., Ershova E.S., Kostyuk G.P., Zakharova N.V., Gorbachevskaya N.L., Kostyuk S.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.journalpsychiatry.com/jour/article/view/341Цель работы

Цель работы: представить современное состояние и перспективы проводимых авторами исследований биологических основ патогенеза психических заболеваний, в частности, нарушенной регуляции синтеза белков (белковой трансляции) на рибосомах.

Материал и метод

Материал и метод. Материалом обзора служили опубликованные ранее работы коллектива авторов данного обзора, а также других отечественных и зарубежных ученых.

Результаты

Результаты. Рибосомы — цитоплазматические органеллы, осуществляющие синтез белков на матричных РНК. Основным компонентом рибосом являются рибосомные РНК (рРНК). Рибосомные гены кодируют молекулы 18S, 5.8S и 28S рРНК. В геноме человека рибосомные гены (РГ) образуют кластеры повторов на пяти парах акроцентрических хромосом, в совокупности называемые рДНК. Число повторов рДНК на диплоидный геном варьирует у разных индивидов от 250 до 670 копий со средним 450. Общее количество рибосомных генов в геноме индивида лимитирует уровень общей трансляции (биосинтеза белков) и имеет различные фенотипические проявления. В обзоре рассматриваются возможные механизмы влияния количества копий рибосомных генов на развитие таких психических заболеваний как шизофрения и расстройства аутистического спектра (РАС).

Выводы

Выводы. Количество копий транскрибируемых рибосомных генов (генов рРНК) является вероятным фактором патогенеза таких психических заболеваний как шизофрения и РАС. Факты повышенной копийности РГ при шизофрении и пониженной их копийности при ревматоидном артрите (РА) могут объяснять известный феномен отрицательной коморбидности этих двух состояний. Выдвинута гипотеза о том, что малое количество работающих РГ в геноме индивида может нивелировать влияние мутаций сигнального пути mTOR, вызывающих синдромальные формы аутизма, и предложены различные пути проверки данной гипотезы.

The objective of the work was to present the current state and prospects of the research of biological of biological phenomena being examined by the authors, which underlie the pathogenesis of mental disorders, including upregulated protein synthesis (translation process) on the ribosomes.

Material and methods

Material and methods: the review is based on previous articles published by the authors of this review and other domestic and foreign scientists.

Results

Results. Ribosomes are cytoplasmic organelles that perform protein biosynthesis on messenger RNA. The major components of the ribosome are ribosomal RNA (rRNA). Human ribosomal genes code for the molecules of 18S, 5.8S, and 28S rRNA. In human genome, ribosomal genes (RG) form clusters of tandem repeats on the five pairs of acrocentric chromosomes termed rDNA. The rDNA copy number per diploid genome in different subjects varies from 250 to 670 copies with a mean of 450. The quantity of ribosomal genes in the individual genomelimits thelevel of total translation (protein biosynthesis) and has various phenotypic manifestations. The review considers possible mechanisms of influence of the copy number of ribosomal genes on the development of such mental disorders as schizophrenia and autistic spectrum disorders (ASD).

Conclusions

Conclusions: the copy number of transcribed ribosomal genes (genes for rRNA) is a possible factor of pathogenesis of such mental disorders as schizophrenia and ASD. The facts of high RG copy number in schizophrenia andlow RG copy number in rheumatoid arthritis can explain the well-known phenomenon of negative comorbidity of these two conditions. A hypothesis was put forward that alow copy number of transccribed RG in an individual genome can neutralize the impact of the mutations in mTOR signalling pathway, which evoke syndromal forms of autism, and various ways to check up the hypothesis were suggested.

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