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Ribosomal biogenesis as an emerging target of neurodevelopmental pathologies
Author(s) -
Hetman Michal,
Slomnicki Lukasz P.
Publication year - 2019
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14576
Subject(s) - ribosome biogenesis , biology , neurodegeneration , microcephaly , neuroscience , biogenesis , ribosomal protein , neurogenesis , nucleolus , microbiology and biotechnology , ribosome , genetics , gene , rna , medicine , pathology , disease , nucleus
Development of the nervous system is carried out by complex gene expression programs that are regulated at both transcriptional and translational level. In addition, quality control mechanisms such as the TP 53‐mediated apoptosis or neuronal activity‐stimulated survival ensure successful neurogenesis and formation of functional circuitries. In the nucleolus, production of ribosomes is essential for protein synthesis. In addition, it participates in chromatin organization and regulates the TP 53 pathway via the ribosomal stress response. Its tight regulation is required for maintenance of genomic integrity. Mutations in several ribosomal components and trans‐acting ribosomal biogenesis factors result in neurodevelopmental syndromes that present with microcephaly, autism, intellectual deficits and/or progressive neurodegeneration. Furthermore, ribosomal biogenesis is perturbed by exogenous factors that disrupt neurodevelopment including alcohol or Zika virus. In this review, we present recent literature that argues for a role of dysregulated ribosomal biogenesis in pathogenesis of various neurodevelopmental syndromes. We also discuss potential mechanisms through which such dysregulation may lead to cellular pathologies of the developing nervous system including insufficient proliferation and/or loss of neuroprogenitors cells, apoptosis of immature neurons, altered neuronal morphogenesis, and neurodegeneration.