Stress granule subtypes: an emerging link to neurodegeneration

Advani, Vivek M.; Ivanov, Pavel

doi:10.1007/s00018-020-03565-0

Cited by 81 publications

(86 citation statements)

References 207 publications

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“…These tetramolecular rG4–tiRNAs target protein synthesis by inhibition of cap-dependent translation via direct interaction with the translation initiation factor eIF4G (Figure 6E ) ( 180 ). As a consequence of translation inhibition, cells promote the formation of Stress Granules (SGs), membraneless cytoplasmic foci with pro-survival functions ( 181 , 182 ).…”

Section: Proposed Functions Of Rna G-quadruplexes In Regulation Of Gementioning

confidence: 99%

Properties and biological impact of RNA G-quadruplexes: from order to turmoil and back

Kharel

Becker

Цветков

et al. 2020

Nucleic Acids Research

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115

130

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Guanine-quadruplexes (G4s) are non-canonical four-stranded structures that can be formed in guanine (G) rich nucleic acid sequences. A great number of G-rich sequences capable of forming G4 structures have been described based on in vitro analysis, and evidence supporting their formation in live cells continues to accumulate. While formation of DNA G4s (dG4s) within chromatin in vivo has been supported by different chemical, imaging and genomic approaches, formation of RNA G4s (rG4s) in vivo remains a matter of discussion. Recent data support the dynamic nature of G4 formation in the transcriptome. Such dynamic fluctuation of rG4 folding-unfolding underpins the biological significance of these structures in the regulation of RNA metabolism. Moreover, rG4-mediated functions may ultimately be connected to mechanisms underlying disease pathologies and, potentially, provide novel options for therapeutics. In this framework, we will review the landscape of rG4s within the transcriptome, focus on their potential impact on biological processes, and consider an emerging connection of these functions in human health and disease.

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Section: Proposed Functions Of Rna G-quadruplexes In Regulation Of Gementioning

confidence: 99%

Properties and biological impact of RNA G-quadruplexes: from order to turmoil and back

Kharel

Becker

Цветков

et al. 2020

Nucleic Acids Research

Self Cite

115

130

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“…Exposure to various stresses, such as heat shock, oxidative stress, and endoplasmic reticulum stress, induces formation of stress granules, which are dynamic assemblies of proteins and RNAs [ 50 ]. Stress granules are membrane-less organelles that contain translationally stalled mRNAs associated with translation initiation factors and multiple RNA-binding proteins, suggesting that stress granules regulate mRNA translation and stability and protect from environmental stresses [ 51 , 52 ]. Recent reports have indicated that variations linked to ALS-FTD in TDP-43, FUS, TIA-1, and C9 or f72 cause abnormal stress granule assembly and disassembly.…”

Section: Neurodegenerative Diseases and Protein Aggregatesmentioning

confidence: 99%

Ubiquitin, Autophagy and Neurodegenerative Diseases

Watanabe

Taguchi

Tanaka

2020

Cells

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Ubiquitin signals play various roles in proteolytic and non-proteolytic functions. Ubiquitin signals are recognized as targets of the ubiquitin–proteasome system and the autophagy–lysosome pathway. In autophagy, ubiquitin signals are required for selective incorporation of cargoes, such as proteins, organelles, and microbial invaders, into autophagosomes. Autophagy receptors possessing an LC3-binding domain and a ubiquitin binding domain are involved in this process. Autophagy activity can decline as a result of genetic variation, aging, or lifestyle, resulting in the onset of various neurodegenerative diseases. This review summarizes the selective autophagy of neurodegenerative disease-associated protein aggregates via autophagy receptors and discusses its therapeutic application for neurodegenerative diseases.

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“…Among these several types of RNA granules, SGs are specialized cytoplasmic membraneless RNA granules, which are composed of SG core components including untranslated polyadenylated RNAs, RNA-binding proteins including poly-A binding protein (PABP), T-cell intracellular antigen1 (TIA-1), pre-initiation complex (PIC), and 40S ribosomal subunits, involved in pausing mRNA translation upon various cellular stresses ( Decker and Parker, 2012 ). Although SG core components are common between subtypes of SGs, SG components are very heterogenous depending on cellular stress, or their subcellular localization ( Aulas et al, 2017 ; Advani and Ivanov, 2020 ; Boncella et al, 2020 ). Several RNA-binding proteins, including SG nucleators or auxiliary factors, could contribute to the dynamic assembly or disassembly of SGs.…”

Section: Stress Granulesmentioning

confidence: 99%

“…However, many RNA-binding proteins related to SGs have been reported to regulate local protein synthesis in axon and dendrites to normalize neuronal signaling. Moreover, non-dividing neurons with highly polarized structures are believed to be more vulnerable to many acute cellular stresses, including oxidative, osmotic, proteotoxic, and chronic stresses, leading to an impairment of local translation and neuronal functions ( Shelkovnikova et al, 2017 ; Advani and Ivanov, 2020 ).…”

Section: Neuronal Transient Stress Granules As Dr Jekyllmentioning

confidence: 99%

“…Neuronal SGs are believed to have pro-survival roles upon various cellular stresses. Indeed, many mutations in several proteins related to SGs have been linked to various neurodegenerative diseases, including amyotrophic lateral sclerosis ( Ryan and Fawzi, 2019 ; Wolozin and Ivanov, 2019 ; Advani and Ivanov, 2020 ). These mutations are found in aggregation-prone PLDs, LCDs, IDRs, and RNA-binding motifs within many RNA-binding proteins.…”

Section: Abnormal Persistent Sgs In Neurodegenerative Diseases: Mr Hmentioning

confidence: 99%

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Dr. Jekyll and Mr. Hyde? Physiology and Pathology of Neuronal Stress Granules

Jeon

Lee

2021

Front. Cell Dev. Biol.

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Stress granules (SGs) are membraneless cytosolic granules containing dense aggregations of RNA-binding proteins and RNAs. They appear in the cytosol under stress conditions and inhibit the initiation of mRNA translation. SGs are dynamically assembled under stressful conditions and rapidly disassembled after stress removal. They are heterogeneous in their RNA and protein content and are cell type- and stress-specific. In post-mitotic neurons, which do not divide, the dynamics of neuronal SGs are tightly regulated, implying that their dysregulation leads to neurodegeneration. Mutations in RNA-binding proteins are associated with SGs. SG components accumulate in cytosolic inclusions in many neurodegenerative diseases, such as frontotemporal dementia and amyotrophic lateral sclerosis. Although SGs primarily mediate a pro-survival adaptive response to cellular stress, abnormal persistent SGs might develop into aggregates and link to the pathogenesis of diseases. In this review, we present recent advances in the study of neuronal SGs in physiology and pathology, and discuss potential therapeutic approaches to remove abnormal, persistent SGs associated with neurodegeneration.

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Stress granule subtypes: an emerging link to neurodegeneration

Cited by 81 publications

References 207 publications

Properties and biological impact of RNA G-quadruplexes: from order to turmoil and back

Properties and biological impact of RNA G-quadruplexes: from order to turmoil and back

Ubiquitin, Autophagy and Neurodegenerative Diseases

Dr. Jekyll and Mr. Hyde? Physiology and Pathology of Neuronal Stress Granules

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