scholarly journals Arabidopsis CALMODULIN-LIKE 38 Regulates Hypoxia-Induced Autophagy of SUPPRESSOR OF GENE SILENCING 3 Bodies

2021 ◽  
Vol 12 ◽  
Author(s):  
Sterling Field ◽  
William Craig Conner ◽  
Daniel M. Roberts
Keyword(s):  
Gene Silencing ◽  
Mrna Translation ◽  
Stress Granules ◽  
Stress Granule ◽  
Calcium Sensor ◽  
In Planta ◽  
Hypoxia Stress ◽  
Induced Stress ◽  
Submergence Stress ◽  
Sensor Protein

During the energy crisis associated with submergence stress, plants restrict mRNA translation and rapidly accumulate stress granules that act as storage hubs for arrested mRNA complexes. One of the proteins associated with hypoxia-induced stress granules in Arabidopsis thaliana is the calcium-sensor protein CALMODULIN-LIKE 38 (CML38). Here, we show that SUPPRESSOR OF GENE SILENCING 3 (SGS3) is a CML38-binding protein, and that SGS3 and CML38 co-localize within hypoxia-induced RNA stress granule-like structures. Hypoxia-induced SGS3 granules are subject to turnover by autophagy, and this requires both CML38 as well as the AAA+-ATPase CELL DIVISION CYCLE 48A (CDC48A). CML38 also interacts directly with CDC48A, and CML38 recruits CDC48A to CML38 granules in planta. Together, this work demonstrates that SGS3 associates with stress granule-like structures during hypoxia stress that are subject to degradation by CML38 and CDC48-dependent autophagy. Further, the work identifies direct regulatory targets for the hypoxia calcium-sensor CML38, and suggest that CML38 association with stress granules and associated regulation of autophagy may be part of the RNA regulatory program during hypoxia stress.

scholarly journals The Arabidopsis Calcium Sensor Calmodulin-like 38 Regulates Stress Granule Autophagy and Dynamics during Low Oxygen Stress and Re-aeration Recovery

2021 ◽  
Author(s):  
Sterling Field ◽  
Whitney Gulledge ◽  
Daniel M. Roberts
Keyword(s):  
Stress Granules ◽  
Recovery Phase ◽  
Calcium Sensor ◽  
Low Oxygen ◽  
Oxygen Stress ◽  
Hypoxia Response ◽  
Submergence Stress ◽  
Anaerobic Stress ◽  
Protein Particles ◽  
Two Phases

AbstractIn response to the energy crisis resulting from submergence stress and hypoxia, Arabidopsis limits non-essential mRNAs translation, and accumulate cytosolic stress granules (SG). SGs are phase-separated mRNA-protein particles that partition transcripts for various fates: storage, degradation, or return to translation after stress alleviation. Here, it is shown that RNA stress granules are dynamically regulated during hypoxia stress and aerobic recovery via two phases of autophagy that require the AAA+ ATPase CDC48 and the calcium sensor Calmodulin-like 38 (CML38). CML38 is a core hypoxia response-protein that associates with hypoxia-induced SGs. We show that CML38 is essential for SG autophagy during extended hypoxia. Further, cml38 mutants show disorganized SG morphology during extended hypoxia, suggesting a role in SG formation and maintenance. We also show that upon the return of aerobic conditions, intracellular calcium and CML38 are necessary for SG breakdown and turnover, and for upregulating autophagy. cml38 mutants not only lose these responses, but also have aberrant, sustained autophagosome accumulation during the reoxygenation recovery phase. The findings suggest that CDC48 RNA granule autophagy (“granulophagy”) is conserved in plants, and that the hypoxia-induced calcium sensor CML38 regulates SG autophagy during anaerobic stress as well as during the reprogramming phase associated with reoxygenation.

scholarly journals HIV-1 Gag Blocks Selenite-Induced Stress Granule Assembly by Altering the mRNA Cap-Binding Complex

mBio ◽  
2016 ◽  
Vol 7 (2) ◽  
Author(s):  
Alessandro Cinti ◽  
Valerie Le Sage ◽  
Marwan Ghanem ◽  
Andrew J. Mouland
Keyword(s):  
Translation Initiation ◽  
Mrna Translation ◽  
Stress Granule ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Type Ii ◽  
Gag Protein ◽  
Induced Stress ◽  
Important Host ◽  
Hiv 1

ABSTRACT Stress granules (SGs) are dynamic accumulations of stalled preinitiation complexes and translational machinery that assemble under stressful conditions. Sodium selenite (Se) induces the assembly of noncanonical type II SGs that differ in morphology, composition, and mechanism of assembly from canonical SGs. Se inhibits translation initiation by altering the cap-binding activity of eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4EBP1). In this work, we show that human immunodeficiency virus type 1 (HIV-1) Gag is able to block the assembly of type II noncanonical SGs to facilitate continued Gag protein synthesis. We demonstrate that expression of Gag reduces the amount of hypophosphorylated 4EBP1 associated with the 5′ cap potentially through an interaction with its target, eIF4E. These results suggest that the assembly of SGs is an important host antiviral defense that HIV-1 has evolved for inhibition through several distinct mechanisms. IMPORTANCE The antiviral stress response is an important host defense that many viruses, including HIV-1, have evolved to evade. Selenite induces a block in translation and leads to stress granule assembly through the sequestration of eIF4E by binding hypophosphorylated 4EBP1. In this work, we demonstrate that in the face of selenite-induced stress, HIV-1 is able to maintain Gag mRNA translation and to elicit a blockade to selenite-induced stress granule assembly by altering the amount of hypophosphorylated 4EBP1 on the 5′ cap.

scholarly journals Eukaryotic Initiation Factor 2α-independent Pathway of Stress Granule Induction by the Natural Product Pateamine A

2006 ◽  
Vol 281 (43) ◽  
pp. 32870-32878 ◽  
Author(s):  
Yongjun Dang ◽  
Nancy Kedersha ◽  
Woon-Kai Low ◽  
Daniel Romo ◽  
Myriam Gorospe ◽  
...  
Keyword(s):  
Translation Initiation ◽  
Stress Granules ◽  
Stress Granule ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Granule Formation ◽  
Eukaryotic Translation ◽  
Induced Stress ◽  
Eukaryotic Translation Initiation ◽  
Pateamine A

Stress granules are aggregates of small ribosomal subunits, mRNA, and numerous associated RNA-binding proteins that include several translation initiation factors. Stress granule assembly occurs in the cytoplasm of higher eukaryotic cells under a wide variety of stress conditions, including heat shock, UV irradiation, hypoxia, and exposure to arsenite. Thus far, a unifying principle of eukaryotic initiation factor 2α phosphorylation prior to stress granule formation has been observed from the majority of experimental evidence. Pateamine A, a natural product isolated from marine sponge, was recently reported to inhibit eukaryotic translation initiation and induce the formation of stress granules. In this report, the protein composition and fundamental progression of stress granule formation and disassembly induced by pateamine A was found to be similar to that for arsenite. However, pateamine A-induced stress granules were more stable and less prone to disassembly than those formed in the presence of arsenite. Most significantly, pateamine A induced stress granules independent of eukaryotic initiation factor 2α phosphorylation, suggesting an alternative mechanism of formation from that previously described for other cellular stresses. Taking into account the known inhibitory effect of pateamine A on eukaryotic translation initiation, a model is proposed to account for the induction of stress granules by pateamine A as well as other stress conditions through perturbation of any steps prior to the rejoining of the 60S ribosomal subunit during the entire translation initiation process.

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

2021 ◽  
Author(s):  
Youngdae Gwon ◽  
Brian A. Maxwell ◽  
Regina-Maria. Kolaitis ◽  
Peipei Zhang ◽  
Hong Joo Kim ◽  
...  
Keyword(s):  
Phase Separation ◽  
Heat Shock ◽  
Percolation Threshold ◽  
Specific Interaction ◽  
Interaction Network ◽  
Stress Granules ◽  
Stress Granule ◽  
Induced Stress ◽  
Central Protein ◽  
Specific Manner

AbstractStress granules are dynamic, reversible condensates composed of RNA and protein that assemble in response to a variety of stressors and are normally disassembled after stress is removed. Whereas the composition of stress granules and the mechanisms underlying their assembly have been extensively studied, far less is known about the mechanisms that govern disassembly. Impaired disassembly has been implicated in some diseases. Here we report that stress granule disassembly is context-dependent and, in the setting of heat shock, requires ubiquitination of G3BP1, the central protein within the stress granule RNA-protein network. Ubiquitinated G3BP1 interacts with the ER-resident protein FAF2, which engages the ubiquitin-dependent segregase p97/VCP. Targeting G3BP1 enables the stress granule-specific interaction network to fall below the percolation threshold for phase separation, which causes disassembly.One Sentence SummaryUbiquitination of G3BP1 mediates FAF2- and p97/VCP-dependent disassembly of heat-induced stress granules

scholarly journals Respiratory Syncytial Virus Induces Host RNA Stress Granules To Facilitate Viral Replication

2010 ◽  
Vol 84 (23) ◽  
pp. 12274-12284 ◽  
Author(s):  
Michael E. Lindquist ◽  
Aaron W. Lifland ◽  
Thomas J. Utley ◽  
Philip J. Santangelo ◽  
James E. Crowe
Keyword(s):  
Respiratory Syncytial Virus ◽  
Inclusion Bodies ◽  
Binding Protein ◽  
Mrna Translation ◽  
Stress Granules ◽  
Stress Granule ◽  
Granule Formation ◽  
Infected Cells ◽  
Viral Inclusion ◽  
Syncytial Virus

ABSTRACT Mammalian cell cytoplasmic RNA stress granules are induced during various conditions of stress and are strongly associated with regulation of host mRNA translation. Several viruses induce stress granules during the course of infection, but the exact function of these structures during virus replication is not well understood. In this study, we showed that respiratory syncytial virus (RSV) induced host stress granules in epithelial cells during the course of infection. We also showed that stress granules are distinct from cytoplasmic viral inclusion bodies and that the RNA binding protein HuR, normally found in stress granules, also localized to viral inclusion bodies during infection. Interestingly, we demonstrated that infected cells containing stress granules also contained more RSV protein than infected cells that did not form inclusion bodies. To address the role of stress granule formation in RSV infection, we generated a stable epithelial cell line with reduced expression of the Ras-GAP SH3 domain-binding protein (G3BP) that displayed an inhibited stress granule response. Surprisingly, RSV replication was impaired in these cells compared to its replication in cells with intact G3BP expression. In contrast, knockdown of HuR by RNA interference did not affect stress granule formation or RSV replication. Finally, using RNA probes specific for RSV genomic RNA, we found that viral RNA predominantly localized to viral inclusion bodies but a small percentage also interacted with stress granules during infection. These results suggest that RSV induces a host stress granule response and preferentially replicates in host cells that have committed to a stress response.

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 Puumala and Andes Orthohantaviruses Cause Transient Protein Kinase R-Dependent Formation of Stress Granules

2019 ◽  
Vol 94 (3) ◽  
Author(s):  
Wanda Christ ◽  
Janne Tynell ◽  
Jonas Klingström
Keyword(s):  
Protein Kinase ◽  
Host Cell ◽  
Stress Responses ◽  
Stress Granules ◽  
Cell Stress ◽  
Stress Granule ◽  
Hantavirus Infection ◽  
Stress Signaling ◽  
Protein Kinase R ◽  
Granule Formation

ABSTRACT Virus infection frequently triggers host cell stress signaling resulting in translational arrest; as a consequence, many viruses employ means to modulate the host stress response. Hantaviruses are negative-sense, single-stranded RNA viruses known to inhibit host innate immune responses and apoptosis, but their impact on host cell stress signaling remains largely unknown. In this study, we investigated activation of host cell stress responses during hantavirus infection. We show that hantavirus infection causes transient formation of stress granules (SGs) but does so in only a limited proportion of infected cells. Our data indicate some cell type-specific and hantavirus species-specific variability in SG prevalence and show SG formation to be dependent on the activation of protein kinase R (PKR). Hantavirus infection inhibited PKR-dependent SG formation, which could account for the transient nature and low prevalence of SG formation observed during hantavirus infection. In addition, we report only limited colocalization of hantaviral proteins or RNA with SGs and show evidence indicating hantavirus-mediated inhibition of PKR-like endoplasmic reticulum (ER) kinase (PERK). IMPORTANCE Our work presents the first report on stress granule formation during hantavirus infection. We show that hantavirus infection actively inhibits stress granule formation, thereby escaping the detrimental effects on global translation imposed by host stress signaling. Our results highlight a previously uncharacterized aspect of hantavirus-host interactions with possible implications for how hantaviruses are able to cause persistent infection in natural hosts and for pathogenesis.

Hippocampal expression of the calcium sensor protein visinin-like protein-1 in schizophrenia

Neuroreport ◽  
2002 ◽  
Vol 13 (4) ◽  
pp. 393-396 ◽  
Author(s):  
Hans-Gert Bernstein ◽  
Karl-Heinz Braunewell ◽  
Christina Spilker ◽  
Peter Danos ◽  
Bruno Baumann ◽  
...  
Keyword(s):  
Calcium Sensor ◽  
Sensor Protein

scholarly journals Translationally Repressed mRNA Transiently Cycles through Stress Granules during Stress

2008 ◽  
Vol 19 (10) ◽  
pp. 4469-4479 ◽  
Author(s):  
Stephanie Mollet ◽  
Nicolas Cougot ◽  
Ania Wilczynska ◽  
François Dautry ◽  
Michel Kress ◽  
...  
Keyword(s):  
Residence Time ◽  
Kinetic Data ◽  
Stress Granules ◽  
Stress Relief ◽  
Mrna Degradation ◽  
Stress Granule ◽  
Storage Site ◽  
Direct Role ◽  
Close Proximity

In mammals, repression of translation during stress is associated with the assembly of stress granules in the cytoplasm, which contain a fraction of arrested mRNA and have been proposed to play a role in their storage. Because physical contacts are seen with GW bodies, which contain the mRNA degradation machinery, stress granules could also target arrested mRNA to degradation. Here we show that contacts between stress granules and GW bodies appear during stress-granule assembly and not after a movement of the two preassembled structures. Despite this close proximity, the GW body proteins, which in some conditions relocalize in stress granules, come from cytosol rather than from adjacent GW bodies. It was previously reported that several proteins actively traffic in and out of stress granules. Here we investigated the behavior of mRNAs. Their residence time in stress granules is brief, on the order of a minute, although stress granules persist over a few hours after stress relief. This short transit reflects rapid return to cytosol, rather than transfer to GW bodies for degradation. Accordingly, most arrested mRNAs are located outside stress granules. Overall, these kinetic data do not support a direct role of stress granules neither as storage site nor as intermediate location before degradation.

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