scholarly journals Stress granules regulate stress-induced paraspeckle assembly

2019 ◽  
Vol 218 (12) ◽  
pp. 4127-4140 ◽  
Author(s):  
Haiyan An ◽  
Jing Tong Tan ◽  
Tatyana A. Shelkovnikova
Keyword(s):  
Stress Granules ◽  
Inhibitory Effect ◽  
Eukaryotic Cells ◽  
Negative Regulators ◽  
Multiple Protein ◽  
Different Types ◽  
Positive Regulators ◽  
Protein Components ◽  
Rnp Granules ◽  
Lateral Sclerosis

Eukaryotic cells contain a variety of RNA-protein macrocomplexes termed RNP granules. Different types of granules share multiple protein components; however, the crosstalk between spatially separated granules remains unaddressed. Paraspeckles and stress granules (SGs) are prototypical RNP granules localized exclusively in the nucleus and cytoplasm, respectively. Both granules are implicated in human diseases, such as amyotrophic lateral sclerosis. We characterized the composition of affinity-purified paraspeckle-like structures and found a significant overlap between the proteomes of paraspeckles and SGs. We further show that paraspeckle hyperassembly is typical for cells subjected to SG-inducing stresses. Using chemical and genetic disruption of SGs, we demonstrate that formation of microscopically visible SGs is required to trigger and maintain stress-induced paraspeckle assembly. Mechanistically, SGs may sequester negative regulators of paraspeckle formation, such as UBAP2L, alleviating their inhibitory effect on paraspeckles. Our study reveals a novel function for SGs as positive regulators of nuclear RNP granule assembly and suggests a role for disturbed SG-paraspeckle crosstalk in human disease.

scholarly journals Ubiquitination of G3BP1 mediates stress granule disassembly in a context-specific manner

Science ◽  
2021 ◽  
Vol 372 (6549) ◽  
pp. eabf6548
Author(s):  
Youngdae Gwon ◽  
Brian A. Maxwell ◽  
Regina-Maria Kolaitis ◽  
Peipei Zhang ◽  
Hong Joo Kim ◽  
...  
Keyword(s):  
Specific Interaction ◽  
Interaction Network ◽  
Stress Granules ◽  
Stress Granule ◽  
Eukaryotic Cells ◽  
Central Protein ◽  
Specific Manner ◽  
Cultured Human Cells ◽  
Context Specific ◽  
Lateral Sclerosis

Stress granules are dynamic, reversible condensates composed of RNA and protein that assemble in eukaryotic cells in response to a variety of stressors and are normally disassembled after stress is removed. The composition and assembly of stress granules is well understood, but little is known about the mechanisms that govern disassembly. Impaired disassembly has been implicated in some diseases including amyotrophic lateral sclerosis, frontotemporal dementia, and multisystem proteinopathy. Using cultured human cells, we found that stress granule disassembly was context-dependent: Specifically in the setting of heat shock, disassembly required ubiquitination of G3BP1, the central protein within the stress granule RNA-protein network. We found that ubiquitinated G3BP1 interacted with the endoplasmic reticulum–associated protein FAF2, which engaged the ubiquitin-dependent segregase p97/VCP (valosin-containing protein). Thus, targeting of G3BP1 weakened the stress granule–specific interaction network, resulting in granule disassembly.

scholarly journals Stress Granules and Neurodegenerative Disorders: A Scoping Review

2021 ◽  
Vol 13 ◽  
Author(s):  
Mohammad Reza Asadi ◽  
Marziyeh Sadat Moslehian ◽  
Hani Sabaie ◽  
Abbas Jalaiei ◽  
Soudeh Ghafouri-Fard ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Scoping Review ◽  
Neurodegenerative Disorders ◽  
Bioinformatics Analysis ◽  
Stress Granules ◽  
Inclusion Criteria ◽  
Frontotemporal Degeneration ◽  
Protein Components ◽  
Lateral Sclerosis

Cytoplasmic ribonucleoproteins called stress granules (SGs) are considered as one of the main cellular solutions against stress. Their temporary presence ends with stress relief. Any factor such as chronic stress or mutations in the structure of the components of SGs that lead to their permanent presence can affect their interactions with pathological aggregations and increase the degenerative effects. SGs involved in RNA mechanisms are important factors in the pathophysiology of neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), frontotemporal degeneration (FTD), and Alzheimer's diseases (AD). Although many studies have been performed in the field of SGs and neurodegenerative disorders, so far, no systematic studies have been executed in this field. The purpose of this study is to provide a comprehensive perspective of all studies about the role of SGs in the pathogenesis of neurodegenerative disorders with a focus on the protein ingredients of these granules. This scoping review is based on a six-stage methodology structure and the PRISMA guideline. A systematic search of seven databases for qualified articles was conducted until December 2020. Publications were screened independently by two reviewers and quantitative and qualitative analysis was performed on the extracted data. Bioinformatics analysis was used to plot the network and predict interprotein interactions. In addition, GO analysis was performed. A total of 48 articles were identified that comply the inclusion criteria. Most studies on neurodegenerative diseases have been conducted on ALS, AD, and FTD using human post mortem tissues. Human derived cell line studies have been used only in ALS. A total 29 genes of protein components of SGs have been studied, the most important of which are TDP-43, TIA-1, PABP-1. Bioinformatics studies have predicted 15 proteins to interact with the protein components of SGs, which may be the constituents of SGs. Understanding the interactions between SGs and pathological aggregations in neurodegenerative diseases can provide new targets for treatment of these disorders.

scholarly journals Transcriptome-Wide Comparison of Stress Granules and P-Bodies Reveals that Translation Plays a Major Role in RNA Partitioning

2019 ◽  
Vol 39 (24) ◽  
Author(s):  
Tyler Matheny ◽  
Bhalchandra S. Rao ◽  
Roy Parker
Keyword(s):  
Stress Granules ◽  
Stress Granule ◽  
Dominant Factor ◽  
Differential Centrifugation ◽  
P Bodies ◽  
Translation Repression ◽  
First Approximation ◽  
Rnp Granules ◽  
Interpretation Of Results

ABSTRACT The eukaryotic cytosol contains multiple RNP granules, including P-bodies and stress granules. Three different methods have been used to describe the transcriptome of stress granules or P-bodies, but how these methods compare and how RNA partitioning occurs between P-bodies and stress granules have not been addressed. Here, we compare the analysis of the stress granule transcriptome based on differential centrifugation with and without subsequent stress granule immunopurification. We find that while differential centrifugation alone gives a first approximation of the stress granule transcriptome, this methodology contains nonspecific transcripts that play a confounding role in the interpretation of results. We also immunopurify and compare the RNAs in stress granules and P-bodies under arsenite stress and compare those results to those for the P-body transcriptome described under nonstress conditions. We find that the P-body transcriptome is dominated by poorly translated mRNAs under nonstress conditions, but during arsenite stress, when translation is globally repressed, the P-body transcriptome is very similar to the stress granule transcriptome. This suggests that translation is a dominant factor in targeting mRNAs into both P-bodies and stress granules, and during stress, when most mRNAs are untranslated, the composition of P-bodies reflects this broader translation repression.

scholarly journals Among Commercially Available Fruit Juices, Pomegranate Is the Most Effective Inhibitor of PMS-Trypsin Amyloid-Like Fibrils Formation

2019 ◽  
Vol 14 (6) ◽  
pp. 1934578X1985912
Author(s):  
Phanindra Babu Kasi ◽  
Márta Kotormán
Keyword(s):  
Type 2 Diabetes ◽  
Amyloid Fibrils ◽  
Binding Assay ◽  
Inhibitory Effect ◽  
Fruit Juices ◽  
Pomegranate Juice ◽  
Effective Inhibitor ◽  
Parkinson’S Diseases ◽  
Lateral Sclerosis

The formation of amyloid fibrils is associated with many human illnesses, such as Alzheimer’s, Huntington’s, and Parkinson’s diseases, amyotrophic lateral sclerosis, spongiform encephalitis, type 2 diabetes, and primary and secondary systemic amyloidosis. Nutrition contributes to the prevention of these diseases. The aim of our work was to look for commercially available fruit juices that can inhibit the formation of amyloid fibrils. Of the fruit juices that we examined, that of pomegranate was found to be the most effective inhibitory agent using turbidity measurements and Congo red binding assay. According to our experiments, pomegranate juice reduced the amount of PMS-trypsin amyloid-like fibrils to 3.7% at 5-fold dilution compared with the sample without pomegranate. The inhibitory effect of the pomegranate juice was concentration dependent.

Role of cations in the flocculation of Saccharomyces cerevisiae and discrimination of the corresponding proteins

1991 ◽  
Vol 37 (5) ◽  
pp. 397-403 ◽  
Author(s):  
Hiroshi Kuriyama ◽  
Itaru Umeda ◽  
Harumi Kobayashi
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Surface ◽  
Inhibitory Effect ◽  
Surface Proteins ◽  
Promoting Effect ◽  
Yeast Strains ◽  
Yeast Flocculation ◽  
Different Types ◽  
Anionic Groups

Asexual yeast flocculation was studied using strong flocculents of Saccharomyces cerevisiae. The inhibitory effect of cations on flocculation is considered to be caused by competition between those cations and Ca2+ at the binding site of the Ca2+-requiring protein that is involved in flocculation. Inhibition of flocculation by various cations occurred in the following order: La3+, Sr2+, Ba2+, Mn2+, Al3+, and Na+. Cations such as Mg2+, Co2+, and K+ promoted flocculation. This promoting effect may be based on the reduction of electrostatic repulsive force between cells caused by binding of these cations anionic groups present on the cell surface. In flocculation induced by these cations, trace amounts of Ca2+ excreted on the cell surface may activate the corresponding protein. The ratio of Sr2+/Ca2+ below which cells flocculated varied among strains: for strains having the FLO5 gene, it was 400 to 500; for strains having the FLO1 gene, about 150; and for two alcohol yeast strains, 40 to 50. This suggests that there are several different types of cell surface proteins involved in flocculation in different yeast strains. Key words: yeast, flocculation, protein, cation, calcium.

Apoptosis in late stage Drosophila nurse cells does not require genes within the H99 deficiency

Development ◽  
1998 ◽  
Vol 125 (6) ◽  
pp. 1075-1082 ◽  
Author(s):  
K. Foley ◽  
L. Cooley
Keyword(s):  
Dna Fragmentation ◽  
Late Stage ◽  
Expression Patterns ◽  
Nuclear Material ◽  
Nurse Cells ◽  
Wild Type ◽  
Negative Regulators ◽  
Egg Chambers ◽  
Positive Regulators ◽  
Egg Chamber

We have determined that nurse cells are cleared from the Drosophila egg chamber by apoptosis. DNA fragmentation begins in nurse cells at stage 12, following the completion of cytoplasm transfer from the nurse cells to the oocyte. During stage 13, nurse cells increasingly contain highly fragmented DNA and disappear from the egg chamber concomitantly with the formation of apoptotic vesicles containing highly fragmented nuclear material. In dumpless mutant egg chambers that fail to complete cytoplasm transport from the nurse cells, DNA fragmentation is markedly delayed and begins during stage 13, when the majority of cytoplasm is lost from the nurse cells. These data suggest the presence of cytoplasmic factors in nurse cells that inhibit the initiation of DNA fragmentation. In addition, we have examined the ovarian expression patterns of regulatory genes implicated in Drosophila apoptosis. The positive regulators, reaper (rpr), head involution defective (hid) and grim, as well as the negative regulators, DIAP1 and DIAP2, are transcribed during oogenesis. However, germline clones homozygous for the deficiency Df(3)H99, which deletes rpr, hid and grim, undergo oogenesis in a manner morphologically indistinguishable from wild type, indicating that genes within this region are not necessary for apoptosis in nurse cells.

scholarly journals The catalytic activity of the Ubp3 deubiquitinating protease is required for efficient stress granule assembly inS. cerevisiae

2015 ◽  
pp. MCB.00609-15 ◽  
Author(s):  
Regina Nostramo ◽  
Sapna N. Varia ◽  
Bo Zhang ◽  
Megan M. Emerson ◽  
Paul K. Herman
Keyword(s):  
Catalytic Activity ◽  
Stress Granules ◽  
Eukaryotic Cell ◽  
Stress Granule ◽  
Resting Cells ◽  
Term Survival ◽  
General Role ◽  
Rnp Complex ◽  
Processing Body ◽  
Rnp Granules

The interior of the eukaryotic cell is a highly compartmentalized space containing both membrane-bound organelles and the recently-identified nonmembranous ribonucleoprotein (RNP) granules. This study examines inSaccharomyces cerevisiaethe assembly of one conserved type of the latter compartment, known as the stress granule. Stress granules form in response to particular environmental cues and have been linked to a variety of human diseases, including amyotrophic lateral sclerosis. To further our understanding of these structures, a candidate genetic screen was employed to identify regulators of stress granule assembly in quiescent cells. These studies identified a ubiquitin-specific protease, Ubp3, as having an essential role in the assembly of these RNP granules. This function was not shared by other members of the Ubp protease family and required Ubp3 catalytic activity as well as its interaction with the cofactor, Bre5. Interestingly, the loss of stress granules was correlated with a decrease in the long-term survival of stationary phase cells. This phenotype is similar to that observed in mutants defective for the formation of a related RNP complex, the Processing-body. Altogether, these observations raise the interesting possibility of a general role for these types of cytoplasmic RNP granules in the survival of G0-like resting cells.

scholarly journals Small molecules for modulating protein driven liquid-liquid phase separation in treating neurodegenerative disease

2019 ◽  
Author(s):  
Richard J. Wheeler ◽  
Hyun O. Lee ◽  
Ina Poser ◽  
Arun Pal ◽  
Thom Doeleman ◽  
...  
Keyword(s):  
Phase Separation ◽  
Neurodegenerative Disease ◽  
Stress Granules ◽  
Life Time ◽  
Stress Granule ◽  
Phase Behaviour ◽  
Granule Proteins ◽  
Lateral Sclerosis ◽  
Liquid Liquid Phase Separation

AbstractAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with few avenues for treatment. Many proteins implicated in ALS associate with stress granules, which are examples of liquid-like compartments formed by phase separation. Aberrant phase transition of stress granules has been implicated in disease, suggesting that modulation of phase transitions could be a possible therapeutic route. Here, we combine cell-based and protein-based screens to show that lipoamide, and its related compound lipoic acid, reduce the propensity of stress granule proteins to aggregate in vitro. More significantly, they also prevented aggregation of proteins over the life time of Caenorhabditis elegans. Observations that they prevent dieback of ALS patient-derived (FUS mutant) motor neuron axons in culture and recover motor defects in Drosophila melanogaster expressing FUS mutants suggest plausibility as effective therapeutics. Our results suggest that altering phase behaviour of stress granule proteins in the cytoplasm could be a novel route to treat ALS.

scholarly journals P-selectin mediates Ca(2+)-dependent adhesion of activated platelets to many different types of leukocytes: detection by flow cytometry

Blood ◽  
1992 ◽  
Vol 80 (1) ◽  
pp. 134-142 ◽  
Author(s):  
LG de Bruijne-Admiraal ◽  
PW Modderman ◽  
AE Von dem Borne ◽  
A Sonnenberg
Keyword(s):  
T Cells ◽  
Divalent Cations ◽  
Phosphatidyl Inositol ◽  
Cell Types ◽  
Inhibitory Effect ◽  
Immunofluorescence Assay ◽  
Cd8 Cells ◽  
Activated Platelets ◽  
Selectin Ligands ◽  
Different Types

Abstract Previous studies have shown that thrombin-activated platelets interact through the P-selectin with neutrophils and monocytes. To identify other types of leukocytes capable of such an interaction, eosinophils, basophils, and lymphocytes were isolated from whole blood. Binding of these cells to activated platelets was examined in a double immunofluorescence assay and the results show that activated platelets not only bind to neutrophils and monocytes, but also to eosinophils, basophils, and subpopulations of T lymphocytes. Using monoclonal antibodies (MoAbs) specific for subsets of T cells, we could further demonstrate that the T cells which bind activated platelets are natural killer (NK) cells and an undefined subpopulation of CD4+ and CD8+ cells. All these interactions were dependent on divalent cations and were completely inhibited by an MoAb against P-selectin. Thus, P- selectin mediates the binding of activated platelets to many different types of leukocytes. Studies with leukocytes treated with proteases or neuraminidase have shown that the structures recognized by P-selectin are glycoproteins carrying sialic acid residues. Because the loss of binding of activated platelets to neuraminidase-treated neutrophils was almost complete, but only partial to treated eosinophils, basophils, and monocytes, the latter cell types may have different P-selectin ligands in addition to those present on neutrophils. We found that two previously identified ligands for P-selectin, the oligosaccharides Le(x) and sialyl-Le(x), had little or no inhibitory effect on adhesion of activated platelets to leukocytes and that binding was not inhibited by MoAbs against these oligosaccharides. In addition, there was no correlation between the expression of Le(x) on several cell types and their capacity to bind activated platelets. In contrast, the expression of sialyl-Le(x) on cells was almost perfectly correlated with their ability to bind activated platelets. Thus, while Le(x) cannot be a major ligand for P-selectin, a possible role for sialyl-Le(x) in P- selectin-mediated adhesion processes cannot be dismissed. Finally, activated platelets were found to bind normally to monocytes and neutrophils of patients with paroxysmal nocturnal hemoglobulinuria (PNH) and to neutrophils from which phosphatidyl inositol (PI)-linked proteins had been removed by glycosylphosphatidyl inositol-specific phospholipase C (GPI-PLC) digestion. This suggests that at least part of the P-selectin ligands on these cells are not GPI-anchored.

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