Abstract
Dysregulation of protein translation is emerging as a unifying mechanism in the pathogenesis of many neuronal disorders. Ribosomal RNA (rRNA) and transfer RNA (tRNA) are structural molecules that have complementary and coordinated functions in protein synthesis. Defects in both rRNAs and tRNAs have been described in mammalian brain development, neurological syndromes, and neurodegeneration. In this review, we present the molecular mechanisms that link aberrant rRNA and tRNA transcription, processing and modifications to translation deficits, and neuropathogenesis. We also discuss the interdependence of rRNA and tRNA biosynthesis and how their metabolism brings together proteotoxic stress and impaired neuronal homeostasis.
Keywords:
cellular stress; neurological disorders; protein synthesis; rRNA; tRNA.
Copyright © 2019 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Alzheimer Disease / genetics*
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Alzheimer Disease / metabolism
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Alzheimer Disease / pathology
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Amyotrophic Lateral Sclerosis / genetics*
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Amyotrophic Lateral Sclerosis / metabolism
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Amyotrophic Lateral Sclerosis / pathology
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Animals
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Brain / metabolism
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Brain / pathology
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Disease Models, Animal
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Frontotemporal Dementia / genetics*
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Frontotemporal Dementia / metabolism
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Frontotemporal Dementia / pathology
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Homeostasis / genetics
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Humans
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Huntington Disease / genetics*
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Huntington Disease / metabolism
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Huntington Disease / pathology
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Neurons / metabolism
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Neurons / pathology
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Organelle Biogenesis
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Parkinson Disease / genetics*
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Parkinson Disease / metabolism
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Parkinson Disease / pathology
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Protein Biosynthesis
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RNA, Ribosomal / biosynthesis
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RNA, Ribosomal / genetics*
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RNA, Transfer / biosynthesis
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RNA, Transfer / genetics*
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Ribosomes / genetics
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Ribosomes / metabolism
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Transcription, Genetic
Substances
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RNA, Ribosomal
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RNA, Transfer