Post-translational modifications on RNA-binding proteins: accelerators, brakes, or passengers in neurodegeneration?

Sternburg, Erin L.; Silva, Lara A. Gruijs da; Dormann, Dorothee

doi:10.1016/j.tibs.2021.07.004

Cited by 50 publications

(48 citation statements)

References 140 publications

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“…Concerning the expression of genes, RNA-binding proteins (RBP) have a key role in RNA expression and metabolism. Consequently, the appropriate control of these proteins is critical for cellular health [ 107 ]. Use of a clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9-single guide RNA library and stimulation of cells with paraquat has permitted us to identify CSDE1 and STRAP proteins, which interact with each other and produce sensitivity to OS, and the Pumilio homologues (PUM1 and PUM2), which produce resistance [ 98 ].…”

Section: New Regulators Of Os For Developing Targeted Treatmentsmentioning

confidence: 99%

“…Thus, this study emphasized that the use of genetic screening may allow us to identify RBPs and novel genes regulating the sensitivity to OS. They may be used for developing targeted treatments for OS [ 107 ].…”

Section: New Regulators Of Os For Developing Targeted Treatmentsmentioning

confidence: 99%

“…Another class of novel OS regulators is the circular RNAs (circRNAs) [ 107 , 108 ], endogenous non-coding RNAs characterized by a covalently closed-loop structure generated through a special type of alternative splicing termed back-splicing. At this time, growing evidence has disclosed that circRNAs are evolutionarily conserved across species, stable and resistant to RNase R degradation.…”

Section: New Regulators Of Os For Developing Targeted Treatmentsmentioning

confidence: 99%

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Oxidative Stress in the Pathogenesis of Aorta Diseases as a Source of Potential Biomarkers and Therapeutic Targets, with a Particular Focus on Ascending Aorta Aneurysms

et al. 2022

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Aorta diseases, such as ascending aorta aneurysm (AsAA), are complex pathologies, currently defined as inflammatory diseases with a strong genetic susceptibility. They are difficult to manage, being insidious and silent pathologies whose diagnosis is based only on imaging data. No diagnostic and prognostic biomarkers or markers of outcome have been known until now. Thus, their identification is imperative. Certainly, a deep understanding of the mechanisms and pathways involved in their pathogenesis might help in such research. Recently, the key role of oxidative stress (OS) on the pathophysiology of aorta disease has emerged. Here, we describe and discuss these aspects by revealing some OS pathways as potential biomarkers, their underlying limitations, and potential solutions and approaches, as well as some potential treatments.

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Section: New Regulators Of Os For Developing Targeted Treatmentsmentioning

confidence: 99%

Section: New Regulators Of Os For Developing Targeted Treatmentsmentioning

confidence: 99%

Section: New Regulators Of Os For Developing Targeted Treatmentsmentioning

confidence: 99%

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Oxidative Stress in the Pathogenesis of Aorta Diseases as a Source of Potential Biomarkers and Therapeutic Targets, with a Particular Focus on Ascending Aorta Aneurysms

et al. 2022

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“…The most well characterized PTMs of RBPs are phosphorylation, methylation, acetylation, sumoylation and ubiquitinylation. The first four of these PTMs have been mainly linked to the regulation of RBPs cellular distribution and interactions, while ubiquitinylation is mainly involved in protein degradation and turnover (Sternburg et al, 2022). Recently, all of these PTMs have been described to regulate the LLPS behavior of RBPs and the consequent formation of membraneless-organelles (MLOs), such as stress granules (SGs) or other ribonucleoprotein (RNP) granules (Wiedner and Giudice, 2021).The goal of our research topic is to highlight how PTMs regulate RNA-protein interactions, protein-protein interactions, LLPS of RBPs, and RNP granule formation and dynamics, as well as how altered PTM patterns on RBPs can be linked to human diseases.The review by Velázquez-Cruz et al summarizes the impact that PTMs have on several mammalian RBPs and how an aberrant PTM profile causes an alteration of physiological processes leading to diseases, such as cancer and neurodegenerative disorders.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Editorial: The Role of Protein Post-Translational Modifications in Protein-RNA Interactions and RNP Assemblies

Giambruno

Grzybowska

Fawzi

et al. 2022

Front. Mol. Biosci.

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Editorial on the Research TopicThe Role of Protein Post-Translational Modifications in Protein-RNA Interactions and RNP Assemblies RNA binding proteins (RBPs) are crucial regulators that participate in almost every cellular function by contributing to key biological processes such as transcription, translation, RNA splicing and RNA transport (Gerstberger et al., 2014). Posttranslational modifications (PTMs) control different aspects of RBPs, in particular their cellular localization; their stability and turnover; the ability of RBPs to bind to RNA and other proteins; and the propensity of RBPs to undergo liquid-liquid phase separation (LLPS). The most well characterized PTMs of RBPs are phosphorylation, methylation, acetylation, sumoylation and ubiquitinylation. The first four of these PTMs have been mainly linked to the regulation of RBPs cellular distribution and interactions, while ubiquitinylation is mainly involved in protein degradation and turnover (Sternburg et al., 2022). Recently, all of these PTMs have been described to regulate the LLPS behavior of RBPs and the consequent formation of membraneless-organelles (MLOs), such as stress granules (SGs) or other ribonucleoprotein (RNP) granules (Wiedner and Giudice, 2021).The goal of our research topic is to highlight how PTMs regulate RNA-protein interactions, protein-protein interactions, LLPS of RBPs, and RNP granule formation and dynamics, as well as how altered PTM patterns on RBPs can be linked to human diseases.The review by Velázquez-Cruz et al. summarizes the impact that PTMs have on several mammalian RBPs and how an aberrant PTM profile causes an alteration of physiological processes leading to diseases, such as cancer and neurodegenerative disorders. In particular, alterations of the PTM profile or mutations in post-translationally modified amino acids in RBPs like trans-activating response element DNA-binding protein of 43 kDa (TDP-43), fused in sarcoma (FUS) and heterogeneous nuclear ribonucleoprotein A and B type (hnRNP-A/B) are linked to neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS), as summarized by Farina et al. This aspect has also been covered in a review by Clarke et al. of biochemical and functional characterization of heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), belonging to the hnRNP-A/B subfamily, in both physiological conditions and neurodegenerative diseases; and how PTMs modulate hnRNPA1 molecular functions.Among the numerous PTMs reported so far, arginine methylation, phosphorylation and sumoylation seem to play major roles in the regulation of RBP activities and in particular on their RNA-binding properties. This last aspect is extremely relevant but at the same time challenging

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Regulation of IFN‐γ production by ZFP36L2 in T cells is time‐dependent

Zandhuis,

Guislain,

Popalzij

et al. 2024

Eur J Immunol

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CD8+ T cells kill target cells by releasing cytotoxic molecules and proinflammatory cytokines, such as TNF and IFN‐γ. The magnitude and duration of cytokine production are defined by posttranscriptional regulation, and critical regulator herein are RNA‐binding proteins (RBPs). Although the functional importance of RBPs in regulating cytokine production is established, the kinetics and mode of action through which RBPs control cytokine production are not well understood. Previously, we showed that the RBP ZFP36L2 blocks the translation of preformed cytokine encoding mRNA in quiescent memory T cells. Here, we uncover that ZFP36L2 regulates cytokine production in a time‐dependent manner. T cell‐specific deletion of ZFP36L2 (CD4‐cre) had no effect on T‐cell development or cytokine production during early time points (2–6 h) of T‐cell activation. In contrast, ZFP36L2 specifically dampened the production of IFN‐γ during prolonged T‐cell activation (20–48 h). ZFP36L2 deficiency also resulted in increased production of IFN‐γ production in tumor‐infiltrating T cells that are chronically exposed to antigens. Mechanistically, ZFP36L2 regulates IFN‐γ production at late time points of activation by destabilizing Ifng mRNA in an AU‐rich element‐dependent manner. Together, our results reveal that ZFP36L2 employs different regulatory nodules in effector and memory T cells to regulate cytokine production.

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Post-translational modifications on RNA-binding proteins: accelerators, brakes, or passengers in neurodegeneration?

Cited by 50 publications

References 140 publications

Oxidative Stress in the Pathogenesis of Aorta Diseases as a Source of Potential Biomarkers and Therapeutic Targets, with a Particular Focus on Ascending Aorta Aneurysms

Oxidative Stress in the Pathogenesis of Aorta Diseases as a Source of Potential Biomarkers and Therapeutic Targets, with a Particular Focus on Ascending Aorta Aneurysms

Editorial: The Role of Protein Post-Translational Modifications in Protein-RNA Interactions and RNP Assemblies

Regulation of IFN‐γ production by ZFP36L2 in T cells is time‐dependent

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