Principles of Stress Granules Revealed by Imaging Approaches

Treeck, Briana Van; Parker, Roy

doi:10.1101/cshperspect.a033068

Cited by 46 publications

(35 citation statements)

References 88 publications

(142 reference statements)

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“…Interestingly, other “non-germ” RNP granules, including mammalian P-bodies, stress granules and nucleoli show heterogeneity in their protein distribution within the granules 4,27 . In particular, there is evidence that Xenopus nucleoli consist of different immiscible liquid-like phases that form core-shell arrangement, with Nucleophosmin NPM1 protein phase (shell) enveloping the FIB1 protein clusters (core).…”

Section: Discussionmentioning

confidence: 99%

Protein components of ribonucleoprotein granules from Drosophila germ cells oligomerize and show distinct spatial organization during germline development

Wahiduzzaman

Tindell

et al. 2019

Sci Rep

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The assembly of large RNA-protein granules occurs in germ cells of many animals and these germ granules have provided a paradigm to study structure-functional aspects of similar structures in different cells. Germ granules in Drosophila oocyte’s posterior pole (polar granules) are composed of RNA, in the form of homotypic clusters, and proteins required for germline development. In the granules, Piwi protein Aubergine binds to a scaffold protein Tudor, which contains 11 Tudor domains. Using a super-resolution microscopy, we show that surprisingly, Aubergine and Tudor form distinct clusters within the same polar granules in early Drosophila embryos. These clusters partially overlap and, after germ cells form, they transition into spherical granules with the structural organization unexpected from these interacting proteins: Aubergine shell around the Tudor core. Consistent with the formation of distinct clusters, we show that Aubergine forms homo-oligomers and using all purified Tudor domains, we demonstrate that multiple domains, distributed along the entire Tudor structure, interact with Aubergine. Our data suggest that in polar granules, Aubergine and Tudor are assembled into distinct phases, partially mixed at their “interaction hubs”, and that association of distinct protein clusters may be an evolutionarily conserved mechanism for the assembly of germ granules.

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Section: Discussionmentioning

confidence: 99%

Protein components of ribonucleoprotein granules from Drosophila germ cells oligomerize and show distinct spatial organization during germline development

Wahiduzzaman

Tindell

et al. 2019

Sci Rep

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“…To determine the molecular mechanisms underlying MLO formation and functioning, in vitro studies are indispensable and have already provided tremendous insight into the characteristics and potential roles of MLOs on biomolecular processes [ 9 , 11 , 50 , 76 , 82 , 83 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 ]. In these in vitro experiments, the effects of pH, temperature and ionic strength on phase behavior are generally explored.…”

Section: Organization Of the Crowded Cytosol Through Overcrowded Cmentioning

confidence: 99%

Liquid–Liquid Phase Separation in Crowded Environments

André

Spruijt

2020

IJMS

221

174

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Biomolecular condensates play a key role in organizing cellular fluids such as the cytoplasm and nucleoplasm. Most of these non-membranous organelles show liquid-like properties both in cells and when studied in vitro through liquid–liquid phase separation (LLPS) of purified proteins. In general, LLPS of proteins is known to be sensitive to variations in pH, temperature and ionic strength, but the role of crowding remains underappreciated. Several decades of research have shown that macromolecular crowding can have profound effects on protein interactions, folding and aggregation, and it must, by extension, also impact LLPS. However, the precise role of crowding in LLPS is far from trivial, as most condensate components have a disordered nature and exhibit multiple weak attractive interactions. Here, we discuss which factors determine the scope of LLPS in crowded environments, and we review the evidence for the impact of macromolecular crowding on phase boundaries, partitioning behavior and condensate properties. Based on a comparison of both in vivo and in vitro LLPS studies, we propose that phase separation in cells does not solely rely on attractive interactions, but shows important similarities to segregative phase separation.

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“…Super-resolution fluorescence microscopy analysis of SG combined with biochemical purifications of their components suggest that SG consist of a stable core that can be biochemically purified, surrounded by a shell with highly dynamic components [13]. Among other components, SG consist of mRNA, translation machinery including initiation factors and small ribosomal subunits, RNA binding proteins with disorganised SG-nucleating motifs (TIA-1, FMRP, G3BP), and signaling molecules (e.g., and RACK1) involved in cell death [4].…”

Section: Introductionmentioning

confidence: 99%

Treatment of cancer cells with Lapatinib negatively regulates general translation and induces stress granules formation

et al. 2020

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Stress granules (SG) are cytoplasmic RNA granules that form during various types of stress known to inhibit general translation, including oxidative stress, hypoxia, endoplasmic reticulum stress (ER), ionizing radiations or viral infection. Induction of these SG promotes cell survival in part through sequestration of proapoptotic molecules, resulting in the inactivation of cell death pathways. SG also form in cancer cells, but studies investigating their formation upon treatment with chemotherapeutics are very limited. Here we identified Lapatinib (Tykerb / Tyverb ®), a tyrosine kinase inhibitor used for the treatment of breast cancers as a new inducer of SG in breast cancer cells. Lapatinib-induced SG formation correlates with the inhibition of general translation initiation which involves the phosphorylation of the translation initiation factor eIF2α through the kinase PERK. Disrupting PERK-SG formation by PERK depletion experiments sensitizes resistant breast cancer cells to Lapatinib. This study further supports the assumption that treatment with anticancer drugs activates the SG pathway, which may constitute an intrinsic stress response used by cancer cells to resist treatment.

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Principles of Stress Granules Revealed by Imaging Approaches

Cited by 46 publications

References 88 publications

Protein components of ribonucleoprotein granules from Drosophila germ cells oligomerize and show distinct spatial organization during germline development

Protein components of ribonucleoprotein granules from Drosophila germ cells oligomerize and show distinct spatial organization during germline development

Liquid–Liquid Phase Separation in Crowded Environments

Treatment of cancer cells with Lapatinib negatively regulates general translation and induces stress granules formation

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