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Individual Copy Number of Ribosomal Genes as a Factor of Mental Retardation and Autism Risk and Severity

Autism is a complex multifactorial developmental disorder characterized by deficits in communication and restricted interests, often followed by mental retardation. Autism spectrum disorders (ASD) are caused by defects in miscellaneous molecular mechanisms, many of which remain unclear. But a consid...

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Detalles Bibliográficos
Autor principal: Porokhovnik, Lev
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830322/
https://www.ncbi.nlm.nih.gov/pubmed/31561466
http://dx.doi.org/10.3390/cells8101151
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author Porokhovnik, Lev
author_facet Porokhovnik, Lev
author_sort Porokhovnik, Lev
collection PubMed
description Autism is a complex multifactorial developmental disorder characterized by deficits in communication and restricted interests, often followed by mental retardation. Autism spectrum disorders (ASD) are caused by defects in miscellaneous molecular mechanisms, many of which remain unclear. But a considerable part of the known pathways converges on protein synthesis or degradation processes at different stages in the dendrites, laying the foundation for a concept of disturbed “translational homeostasis” or “proteostasis” in autism. The protein synthesis is conducted on ribosomes, cellular organelles consisting from a complex of riboproteins and a ribosomal RNA (rRNA) framework. The rRNA is encoded by ribosomal genes (RG) existing in multiple copies in the genome. The more copies of RG that are contained in the genome, the higher is the peak (maximum possible) ribosome abundance in the cell. A hypothesis is proposed that the RG copy number, through determining the quantity of ribosomes available in the dendrites, modulates the level of local dendritic translation and thus is a factor of risk and severity of a series of neuropsychiatric disorders caused by aberrant dendritic translation. A carrier of very low copy number of ribosomal genes is expected to have a milder form of ASD than a subject with the same epigenetic and genetic background, but a higher ribosomal gene dosage. Various ways of evaluation and testing the hypothesis on clinical material and animal models are suggested.
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spelling pubmed-68303222019-11-20 Individual Copy Number of Ribosomal Genes as a Factor of Mental Retardation and Autism Risk and Severity Porokhovnik, Lev Cells Hypothesis Autism is a complex multifactorial developmental disorder characterized by deficits in communication and restricted interests, often followed by mental retardation. Autism spectrum disorders (ASD) are caused by defects in miscellaneous molecular mechanisms, many of which remain unclear. But a considerable part of the known pathways converges on protein synthesis or degradation processes at different stages in the dendrites, laying the foundation for a concept of disturbed “translational homeostasis” or “proteostasis” in autism. The protein synthesis is conducted on ribosomes, cellular organelles consisting from a complex of riboproteins and a ribosomal RNA (rRNA) framework. The rRNA is encoded by ribosomal genes (RG) existing in multiple copies in the genome. The more copies of RG that are contained in the genome, the higher is the peak (maximum possible) ribosome abundance in the cell. A hypothesis is proposed that the RG copy number, through determining the quantity of ribosomes available in the dendrites, modulates the level of local dendritic translation and thus is a factor of risk and severity of a series of neuropsychiatric disorders caused by aberrant dendritic translation. A carrier of very low copy number of ribosomal genes is expected to have a milder form of ASD than a subject with the same epigenetic and genetic background, but a higher ribosomal gene dosage. Various ways of evaluation and testing the hypothesis on clinical material and animal models are suggested. MDPI 2019-09-26 /pmc/articles/PMC6830322/ /pubmed/31561466 http://dx.doi.org/10.3390/cells8101151 Text en © 2019 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Hypothesis
Porokhovnik, Lev
Individual Copy Number of Ribosomal Genes as a Factor of Mental Retardation and Autism Risk and Severity
title Individual Copy Number of Ribosomal Genes as a Factor of Mental Retardation and Autism Risk and Severity
title_full Individual Copy Number of Ribosomal Genes as a Factor of Mental Retardation and Autism Risk and Severity
title_fullStr Individual Copy Number of Ribosomal Genes as a Factor of Mental Retardation and Autism Risk and Severity
title_full_unstemmed Individual Copy Number of Ribosomal Genes as a Factor of Mental Retardation and Autism Risk and Severity
title_short Individual Copy Number of Ribosomal Genes as a Factor of Mental Retardation and Autism Risk and Severity
title_sort individual copy number of ribosomal genes as a factor of mental retardation and autism risk and severity
topic Hypothesis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830322/
https://www.ncbi.nlm.nih.gov/pubmed/31561466
http://dx.doi.org/10.3390/cells8101151
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