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MINI REVIEW article
Front. Mol. Neurosci.
Sec. Neuroplasticity and Development
Volume 17 - 2024 |
doi: 10.3389/fnmol.2024.1398048
This article is part of the Research Topic Come as You R(NA): Post-transcriptional Regulation Will Do the Rest View all 10 articles
Crosstalk between ubiquitination and translation in neurodevelopmental disorders
Provisionally accepted- Simons Initiative for the Developing Brain, Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, Scotland, United Kingdom
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: Ubiquitin, translation, Splicing, ribosome, Neurodevelopmental disorders, FMRP, Ube3A
Received: 08 Mar 2024; Accepted: 12 Aug 2024.
Copyright: © 2024 Elu, Subash and R. Louros. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Susana R. Louros, Simons Initiative for the Developing Brain, Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, EH8 9XD, Scotland, United Kingdom
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