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Review
. 2024 Sep 2:17:1398048.
doi: 10.3389/fnmol.2024.1398048. eCollection 2024.

Crosstalk between ubiquitination and translation in neurodevelopmental disorders

Nagore Elu  1   2 , Srividya Subash  1   2 , Susana R Louros  1   2
Affiliations
Review

Crosstalk between ubiquitination and translation in neurodevelopmental disorders

Nagore Elu et al. Front Mol Neurosci. .

Abstract

Ubiquitination is one of the most conserved post-translational modifications and together with mRNA translation contributes to cellular protein homeostasis (proteostasis). Temporal and spatial regulation of proteostasis is particularly important during synaptic plasticity, when translation of specific mRNAs requires tight regulation. Mutations in genes encoding regulators of mRNA translation and in ubiquitin ligases have been associated with several neurodevelopmental disorders. RNA metabolism and translation are regulated by RNA-binding proteins, critical for the spatial and temporal control of translation in neurons. Several ubiquitin ligases also regulate RNA-dependent mechanisms in neurons, with numerous ubiquitination events described in splicing factors and ribosomal proteins. Here we will explore how ubiquitination regulates translation in neurons, from RNA biogenesis to alternative splicing and how dysregulation of ubiquitin signaling can be the underlying cause of pathology in neurodevelopmental disorders, such as Fragile X syndrome. Finally we propose that targeting ubiquitin signaling is an attractive novel therapeutic strategy for neurodevelopmental disorders where mRNA translation and ubiquitin signaling are disrupted.

Keywords: FMRP; UBE3A; neurodevelopmental disorders; ribosome; splicing; translation; ubiquitin.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Ubiquitin signaling as a central regulator of RNA metabolism in the brain. Ubiquitination regulates splicing, through regulation of the spliceosome remodeling; RNA-binding protein abundance and binding partners; translation rates through ribosomal protein ubiquitination and the turnover rates of proteins in the brain. Disruption of these pathways has been implicated in neurodevelopmental disorders, therefore targeting the ubiquitin signaling is a promising new therapeutic strategy.
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Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Simons Initiative for the Developing Brain and by the College of Medicine and Veterinary Medicine, University of Edinburgh.

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