scholarly journals Ubiquitination is essential for recovery of cellular activities after heat shock

Science ◽  
2021 ◽  
Vol 372 (6549) ◽  
pp. eabc3593
Author(s):  
Brian A. Maxwell ◽  
Youngdae Gwon ◽  
Ashutosh Mishra ◽  
Junmin Peng ◽  
Haruko Nakamura ◽  
...  
Keyword(s):  
Heat Stress ◽  
Cultured Cells ◽  
Nucleocytoplasmic Transport ◽  
Stress Granule ◽  
Eukaryotic Cells ◽  
Granule Formation ◽  
Cellular Processes ◽  
Specific Proteins ◽  
Global Increase ◽  
As Stress

Eukaryotic cells respond to stress through adaptive programs that include reversible shutdown of key cellular processes, the formation of stress granules, and a global increase in ubiquitination. The primary function of this ubiquitination is thought to be for tagging damaged or misfolded proteins for degradation. Here, working in mammalian cultured cells, we found that different stresses elicited distinct ubiquitination patterns. For heat stress, ubiquitination targeted specific proteins associated with cellular activities that are down-regulated during stress, including nucleocytoplasmic transport and translation, as well as stress granule constituents. Ubiquitination was not required for the shutdown of these processes or for stress granule formation but was essential for the resumption of cellular activities and for stress granule disassembly. Thus, stress-induced ubiquitination primes the cell for recovery after heat stress.

scholarly journals Ubiquitination is essential for recovery of cellular activities following heat shock

2021 ◽  
Author(s):  
Brian A. Maxwell ◽  
Youngdae Gwon ◽  
Ashutosh Mishra ◽  
Junmin Peng ◽  
Ke Zhang ◽  
...  
Keyword(s):  
Heat Stress ◽  
Heat Shock ◽  
Nucleocytoplasmic Transport ◽  
Stress Granule ◽  
Misfolded Proteins ◽  
Eukaryotic Cells ◽  
Granule Formation ◽  
Cellular Processes ◽  
Different Types ◽  
Global Increase

AbstractEukaryotic cells respond to stress via adaptive programs that include reversible shutdown of key cellular processes, the formation of stress granules, and a global increase in ubiquitination. The primary function of this ubiquitination is generally considered to be tagging damaged or misfolded proteins for degradation. Here we show that different types of stress generate distinct ubiquitination patterns. For heat stress, ubiquitination correlates with cellular activities that are downregulated during stress, including nucleocytoplasmic transport and translation, as well as with stress granule constituents. Ubiquitination is not required for the shutdown of these processes or for stress granule formation, but is essential for resumption of cellular activities and for stress granule disassembly. These findings indicate that stress-induced ubiquitination primes the cell for recovery following heat stress.One Sentence SummaryStress-induced ubiquitination is essential for recovery of cellular activities following heat stress.

scholarly journals Disruption of Stress Granule Formation by the Multifunctional Cricket Paralysis Virus 1A Protein

2016 ◽  
Vol 91 (5) ◽  
Author(s):  
Anthony Khong ◽  
Craig H. Kerr ◽  
Clarence H. L. Yeung ◽  
Kathleen Keatings ◽  
Arabinda Nayak ◽  
...  
Keyword(s):  
Virus Infection ◽  
Stress Granule ◽  
Granule Formation ◽  
Viral Translation ◽  
Content Type ◽  
Cellular Processes ◽  
Cellular Environment ◽  
Viral Yield ◽  
Infected Cells ◽  
Paralysis Virus

ABSTRACT Stress granules (SGs) are cytosolic ribonucleoprotein aggregates that are induced during cellular stress. Several viruses modulate SG formation, suggesting that SGs have an impact on virus infection. However, the mechanisms and impact of modulating SG assembly in infected cells are not completely understood. In this study, we identify the dicistrovirus cricket paralysis virus 1A (CrPV-1A) protein that functions to inhibit SG assembly during infection. Moreover, besides inhibiting RNA interference, CrPV-1A also inhibits host transcription, which indirectly modulates SG assembly. Thus, CrPV-1A is a multifunctional protein. We identify a key R146A residue that is responsible for these effects, and mutant CrPV(R146A) virus infection is attenuated in Drosophila melanogaster S2 cells and adult fruit flies and results in increased SG formation. Treatment of CrPV(R146A)-infected cells with actinomycin D, which represses transcription, restores SG assembly suppression and viral yield. In summary, CrPV-1A modulates several cellular processes to generate a cellular environment that promotes viral translation and replication. IMPORTANCE RNA viruses encode a limited set of viral proteins to modulate an array of cellular processes in order to facilitate viral replication and inhibit antiviral defenses. In this study, we identified a viral protein, called CrPV-1A, within the dicistrovirus cricket paralysis virus that can inhibit host transcription, modulate viral translation, and block a cellular process called stress granule assembly. We also identified a specific amino acid within CrPV-1A that is important for these cellular processes and that mutant viruses containing mutations of CrPV-1A attenuate virus infection. We also demonstrate that the CrPV-1A protein can also modulate cellular processes in human cells, suggesting that the mode of action of CrPV-1A is conserved. We propose that CrPV-1A is a multifunctional, versatile protein that creates a cellular environment in virus-infected cells that permits productive virus infection.

scholarly journals C9orf72 Dipeptide Repeats Inhibit UPF1-Mediated RNA Decay Independent of Stress Granule Formation

2019 ◽  
Author(s):  
Yu Sun ◽  
Aziz Eshov ◽  
Junjie U. Guo
Keyword(s):  
Cultured Cells ◽  
Ectopic Expression ◽  
Stress Granule ◽  
Rna Decay ◽  
Familial Amyotrophic Lateral Sclerosis ◽  
Repeat Region ◽  
Granule Formation ◽  
Nonsense Mediated Decay ◽  
Rna Surveillance ◽  
Lateral Sclerosis

ABSTRACTExpansion of an intronic (GGGGCC)n repeat region within the C9orf72 gene is a major cause of familial amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD). A pathological hallmark in c9ALS/FTD is the accumulation of misprocessed RNAs, which are often targets of RNA surveillance pathways in normal cells. Here we show that nonsense-mediated decay (NMD) and other RNA decay mechanisms involving upstream frameshift 1 (UPF1), collectively referred to as UPF1-mediated RNA decay (UMD), are broadly inhibited in c9ALS/FTD brains. These effects are recapitulated in cultured cells by the ectopic expression of arginine-rich dipeptide repeats (DPRs), poly(GR) and poly(PR). Despite these two DPRs causing the recruitment of UPF1 to stress granules, stress granule formation is neither sufficient nor necessary for UMD inhibition. Our results suggest that UMD inhibition may accelerate the accumulation of deleterious RNAs and polypeptides in c9ALS/FTD.

scholarly journals The UBAP2L ortholog PQN-59 contributes to stress granule assembly and development in C. elegans

2021 ◽  
Author(s):  
Simona Abbatemarco ◽  
Alexandra Bondaz ◽  
Françoise Schwager ◽  
Jing Wang ◽  
Christopher M Hammell ◽  
...  
Keyword(s):  
Stress Granules ◽  
Stress Granule ◽  
Eukaryotic Cells ◽  
Stress Exposure ◽  
Exact Role ◽  
Granule Formation ◽  
Protective Function ◽  
C Elegans ◽  
Ribonucleoprotein Complexes ◽  
Higher Sensitivity

When exposed to stressful conditions, eukaryotic cells respond by inducing the formation of cytoplasmic ribonucleoprotein complexes called stress granules. Stress granules are thought to have a protective function but their exact role is still unclear. Here we use C. elegans to study two proteins that have been shown to be important for stress granule assembly in human cells: PQN-59, the ortholog of human UBAP2L, and GTBP-1, the ortholog of the human G3BP1 and G3BP2 proteins. Both proteins fall into stress granules in the embryo and in the germline when C. elegans is exposed to stressful conditions. None of the two proteins is essential for the assembly of stress induced granules, but the granules formed in absence of PQN-59 or GTBP-1 are less numerous and dissolve faster than the ones formed in control embryos. Despite these differences, pqn-59 or gtbp-1 mutant embryos do not show a higher sensitivity to stress than control embryos. pqn-59 mutants display reduced progeny and a high percentage of embryonic lethality, phenotypes that are not dependent on stress exposure and that are not shared with gtbp-1 mutants. Our data indicate that both GTBP-1 and PQN-59 contribute to stress granule formation but that PQN-59 is, in addition, required for C. elegans development.

scholarly journals Stimulation of Gαq Promotes Stress Granule Formation

2019 ◽  
Author(s):  
Androniqi Qifti ◽  
Lela Jackson ◽  
Ashima Singla ◽  
Osama Garwain ◽  
Suzanne Scarlata
Keyword(s):  
Plasma Membrane ◽  
Mammalian Cells ◽  
Stress Granules ◽  
Stress Granule ◽  
Granule Formation ◽  
Adverse Conditions ◽  
Granule Proteins ◽  
Regulate Protein ◽  
As Stress ◽  
Number Of Particles

ABSTRACTDuring adverse conditions, mammalian cells regulate protein production by carefully sequestering the translation machinery in membraneless organelles referred to as stress granules. Here, we show that activation of Gαq promotes the formation of particles that contain stress granule proteins through a mechanism linked to the presence of phospholipase Cβ1 (PLCβ1). In cells, PLCβ1, the most prominent isoform of PLCβ in neuronal cells, localizes to both the cytoplasm and plasma membrane. We show that a major population of cytosolic PLCβ1 binds to stress granule proteins, such as PABPC1, eIF5A and Ago2. PLCβ1 is activated by Gαq in response to hormones and neurotransmitters and we find that activation of Gαq shifts the cytosolic population of PLCβ1 to the plasma membrane, reducing its association to stress granule proteins. The loss of cytosolic PLCβ1 is accompanied by an increase in the size and number of particles containing PABPC1, G3BP1 or Ago2, and a shift of cytosolic RNAs to larger sizes consistent with cessation of translation. Particles containing stress granule proteins are seen when the cytosolic level of PLCβ1 is lowered by siRNA or by osmotic stress but not cold, heat, oxidative or arsenite stress suggesting that their composition is distinct from those formed from other stresses. Our results fit a simple thermodynamic model in which cytosolic PLCβ1 solubilizes stress granule proteins and its movement to Gαq upon stimulation releases these particles to allow the formation of stress granules. Taken together, our studies show a link between Gαq-coupled signals and translation through stress granule formation.

scholarly journals The Orb6-Sts5 Axis Regulates Stress Granule Formation and Heat Stress Response in Fission Yeast

2021 ◽  
Author(s):  
Robert N. Tams ◽  
Chuan Chen ◽  
Illyce Nuñez ◽  
Patrick Roman Haller ◽  
Fulvia Verde
Keyword(s):  
Heat Stress ◽  
Cell Growth ◽  
Cell Survival ◽  
Rna Binding ◽  
Stress Granules ◽  
Stress Granule ◽  
Granule Formation ◽  
Heat Stress Response ◽  
P Bodies ◽  
Intrinsically Disordered

AbstractThe NDR/LATS family kinases are a subclass of the AGC serine/threonine kinases which are important for morphogenesis and cell growth control. Using the model organismSchizosaccharomyces pombe, we previously reported that the NDR/LATS kinase Orb6 phosphorylates the RNA-binding protein (RBP) Sts5 serine 86 residue on its Intrinsically Disordered Domain (IDD). When dephosphorylated, Sts5 forms ribonucleoprotein (RNP) granules that colocalize with processing bodies (P-Bodies) and translationally repress mRNAs important for polarized cell growth. Here we report that Sts5 puncta colocalize with both P-Bodies and stress granules (SG) in response to glucose starvation, as well as heat, oxidative, and hyperosmotic stress. We find that loss of Sts5 decreases the number of stress granules, indicating that Sts5 has a role in promoting stress granule formation. Conversely, inhibition of Orb6 kinase promotes Sts5 aggregation and stress granule formation. In addition, loss of Sts5 decreases cell survival after heat stress, whereas decreasing Orb6 protein levels or including thests5S86Amutation, which promotes Sts5 aggregation, leads to increased survival. These data indicate that the Orb6-Sts5 axis is not only important for regulation of polarized growth but also for response to environmental stress, as dysregulation of the Orb6-Sts5 axis affects stress granule formation and cell survival.

scholarly journals Musashi-1 maintains blood–testis barrier structure during spermatogenesis and regulates stress granule formation upon heat stress

2015 ◽  
Vol 26 (10) ◽  
pp. 1947-1956 ◽  
Author(s):  
Sun ErLin ◽  
Wei WenJie ◽  
Wang LiNing ◽  
Lu BingXin ◽  
Lei MingDe ◽  
...  
Keyword(s):  
Heat Stress ◽  
Cell Fate ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Stress Granules ◽  
Stress Granule ◽  
Granule Formation ◽  
Associated Proteins ◽  
Blood Testis Barrier

In mouse testes, Musashi-1 (Msi-1) was predominantly expressed in the cytoplasm and nuclei of Sertoli cells. Here we demonstrate that knockdown of Msi-1 in Sertoli cells altered the levels and distribution of blood–testis barrier (BTB)-associated proteins. Moreover, Msi-1 knockdown in vivo disrupted BTB functional structure and spermatogenesis. In addition, we report a novel role of Msi-1 in regulating Sertoli cells survival following heat-induced injury. Endogenous Msi-1 protein in heat-treated Sertoli cells was recruited to stress granules. The formation of stress granules was considerably disrupted, and apoptosis was significantly up-regulated in Msi-1–knockdown Sertoli cells after heat treatment. p-ERK1/2 acted downstream of stress granule formation, and inhibition of p-ERK1/2 signaling triggered Sertoli cell apoptosis upon heat stress. In conclusion, we demonstrate that Msi-1 is critical for constructing a functional BTB structure and maintaining spermatogenesis. We also note a role for Msi-1 in regulating Sertoli cell fate following heat-induced injury, likely through the induction of stress granule formation and subsequent activation of p-ERK1/2 signaling.

scholarly journals PQN-59 and GTBP-1 contribute to stress granule formation but are not essential for their assembly in C. elegans embryos

2021 ◽  
Author(s):  
Simona Abbatemarco ◽  
Alexandra Bondaz ◽  
Francoise Schwager ◽  
Jing Wang ◽  
Christopher M. Hammell ◽  
...  
Keyword(s):  
Stress Granules ◽  
Human Cells ◽  
Embryonic Lethality ◽  
Stress Granule ◽  
Eukaryotic Cells ◽  
Stress Exposure ◽  
Granule Formation ◽  
C Elegans ◽  
Ribonucleoprotein Complexes ◽  
Higher Sensitivity

When exposed to stressful conditions, eukaryotic cells respond by inducing the formation of cytoplasmic ribonucleoprotein complexes called stress granules. Here we use C. elegans to study two proteins that are important for stress granule assembly in human cells: PQN-59, the human UBAP2L ortholog, and GTBP-1, the human G3BP1/2 ortholog. Both proteins assemble into stress granules in the embryo and in the germline when C. elegans is exposed to stressful conditions. None of the two proteins is essential for the assembly of stress-induced granules, as shown by the single and combined depletions by RNAi, and neither pqn-59 nor gtbp-1 mutant embryos show higher sensitivity to stress than control embryos. We find that pqn-59 mutants display reduced progeny and a high percentage of embryonic lethality, phenotypes that are not dependent on stress exposure and that are not shared with gtbp-1 mutants. Our data indicate that, in contrast to human cells, PQN-59 and GTBP-1 are not required for stress granule formation but that PQN-59 is important for C. elegans development.

Picornavirus 2A Protease Disrupts G3BP-eIF4GI Interaction That Initiates Typical Stress Granule Formation

2018 ◽  
Author(s):  
Xiaodan Yang ◽  
Zhulong Hu ◽  
Shanshan Fan ◽  
Qiang Zhang ◽  
Yi Zhong ◽  
...  
Keyword(s):  
Stress Granule ◽  
Granule Formation ◽  
2A Protease
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