The possible role of copy number of ribosomal genes in the development of mental disorders

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

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: 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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