RNA-Binding Proteins as Epigenetic Regulators of Brain Functions and Their Involvement in Neurodegeneration
Abstract
:1. Introduction
2. Post-Transcriptional Regulation of Gene Expression in the Nervous System
2.1. Mechanisms of Controlled RNA Metabolism, Localization, and Translation
2.2. Intrinsically Disordered Regions (IDRs)
2.3. Brain Cell Asymmetry
2.4. RBPs as Regulators of mRNA Pre-Localization in Brain Cells
2.5. RBPs and Neuronal Plasticity
3. Role of RBPs in RNA Sorting to Extracellular Vesicles
3.1. Extracellular Vesicles (EVs): Origin and General Functions
3.2. Roles of EVs in the Nervous System
3.3. Specific Sorting of Molecules to Nascent EVs: Possible Role of RNA-Binding Proteins
4. RBPs and Neurological Diseases
4.1. Amyotrophic Lateral Sclerosis (ALS)
4.1.1. TDP-43
4.1.2. FUS
4.2. Multiple Sclerosis (MS)
4.3. Alzheimer’s Disease (AD)
5. Conclusions and Future Perspectives
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Neurological Disease | RBPs | Predominant Localization in Normal Conditions | Suggested Functions | Tendency to Form Aggregates |
---|---|---|---|---|
Amyotrophic Lateral Sclerosis (SLA) | TDP-43 [334,335,336,337,338,339,340,341,342,343,344,345,346,347,348] FUS [349,350,351,352,353,354,355,356] | Nuclear (neurons) Nuclear (neurons) | -splicing -granule formation -RNA transport and protection [334,335,336,337,346] Processing of different RNAs (among which miRNAs) [352,354] | yes [336,337,338,339,340,341,342,346] RNA binding seems to be protective for aggregation [348] yes [356] |
Multiple Sclerosis (MS) | TDP-43 [364,365,366] HnRNPA1 [364,365,367] HuR | Nuclear (neurons) Nuclear (neurons) Cytoplasm (microglial cells) [368] | see above -different aspects of RNA metabolism [331] -miRNA sorting to EVs [318] | see above yes [383] observed in gliomas [384] |
Alzheimer’s Disease (AD) | Tau | neuronal axons | Main function: regulation of microtubules dynamics [374] Hypothesized functions: -RNA binding [378,379], with a possible effect on splicing [374] | yes Tau has been reported to form complexes with some RBPs, such as Musashi [381] and HnRNPA1 [382] NOTE: RNA can cause conversion in vitro of soluble Tau into paired helical filaments [377] |
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Di Liegro, C.M.; Schiera, G.; Schirò, G.; Di Liegro, I. RNA-Binding Proteins as Epigenetic Regulators of Brain Functions and Their Involvement in Neurodegeneration. Int. J. Mol. Sci. 2022, 23, 14622. https://doi.org/10.3390/ijms232314622
Di Liegro CM, Schiera G, Schirò G, Di Liegro I. RNA-Binding Proteins as Epigenetic Regulators of Brain Functions and Their Involvement in Neurodegeneration. International Journal of Molecular Sciences. 2022; 23(23):14622. https://doi.org/10.3390/ijms232314622
Chicago/Turabian StyleDi Liegro, Carlo Maria, Gabriella Schiera, Giuseppe Schirò, and Italia Di Liegro. 2022. "RNA-Binding Proteins as Epigenetic Regulators of Brain Functions and Their Involvement in Neurodegeneration" International Journal of Molecular Sciences 23, no. 23: 14622. https://doi.org/10.3390/ijms232314622