Stress granules, P-bodies and cancer

Anderson, Paul; Kedersha, Nancy; Ivanov, Pavel

doi:10.1016/j.bbagrm.2014.11.009

Cited by 351 publications

(415 citation statements)

References 171 publications

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“…3). Overall, the fluorescence microscopy results support the proteomics screen and a previous report (34) Stress granules are reported to form under conditions of oxidative stress (24,43,44). We reasoned that oxidative stress could damage DNA, leading to the excision of nuclear or mitochondrial DNA followed by transfer of the excised sequences into the cytoplasm.…”

Section: Resultssupporting

confidence: 72%

“…The proposed G4DNA signaling response to DNA oxidation reported here could be especially valuable to the cell by directly reporting the level of DNA damage to proteins that regulate translation (21,22,24). The fact that many cells can readily take up G4DNA indicates that this mechanism may also allow the cell to respond to its external environment as well as internal stress (67,72).…”

Section: Discussionmentioning

confidence: 99%

“…DHX36 is a multifunctional enzyme involved in transcription (30) and translation (31) and has been suggested to serve as a sensor for DNA in the cytoplasm (32). Surprisingly, other enriched proteins are ELAV1/HUR, YB-1/ YBOX1, and TIA1, as well as other proteins known to regulate translation and assemble into stress granules (21,24). Stress granules are cytosolic ribonucleoprotein aggregates of stalled translation complexes that form in response to various stresses.…”

Section: Resultsmentioning

confidence: 99%

“…G4DNA structures from damaged G-rich sequences provide a direct mechanism for the cell to sense oxidative stress-induced DNA damage (56). The formation of stress granules is known to modulate RNA translation during oxidative stress (24,57). Although the translation of some mRNAs is stalled by stress granule formation, other transcripts are actively excluded from stress granules (23), making the effects of stress granule formation on individual protein levels difficult to predict.…”

Section: Discussionmentioning

confidence: 99%

“…They have been proposed to function as sites of mRNA triage (23), which govern the composition and function of ribonucleoprotein complexes in order to determine whether individual mRNAs are stored, degraded, or translation is reinitiated. There are clear connections between stress granule function and the pathogenesis of cancer (24). The pathway proposed in this work provides a new mechanism by which cells can respond to the effects of DNA damage during oxidative stress.…”

mentioning

confidence: 98%

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Evidence That G-quadruplex DNA Accumulates in the Cytoplasm and Participates in Stress Granule Assembly in Response to Oxidative Stress

Byrd¹,

Zybailov

Maddukuri³

et al. 2016

Journal of Biological Chemistry

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Cells engage numerous signaling pathways in response to oxidative stress that together repair macromolecular damage or direct the cell toward apoptosis. As a result of DNA damage, mitochondrial DNA or nuclear DNA has been shown to enter the cytoplasm where it binds to "DNA sensors," which in turn initiate signaling cascades. Here we report data that support a novel signaling pathway in response to oxidative stress mediated by specific guanine-rich sequences that can fold into G-quadruplex DNA (G4DNA). In response to oxidative stress, we demonstrate that sequences capable of forming G4DNA appear at increasing levels in the cytoplasm and participate in assembly of stress granules. Identified proteins that bind to endogenous G4DNA in the cytoplasm are known to modulate mRNA translation and participate in stress granule formation. Consistent with these findings, stress granule formation is known to regulate mRNA translation during oxidative stress. We propose a signaling pathway whereby cells can rapidly respond to DNA damage caused by oxidative stress. Guanine-rich sequences that are excised from damaged genomic DNA are proposed to enter the cytoplasm where they can regulate translation through stress granule formation. This newly proposed role for G4DNA provides an additional molecular explanation for why such sequences are prevalent in the human genome.

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Section: Resultssupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 98%

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Evidence That G-quadruplex DNA Accumulates in the Cytoplasm and Participates in Stress Granule Assembly in Response to Oxidative Stress

Byrd¹,

Zybailov

Maddukuri³

et al. 2016

Journal of Biological Chemistry

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Malonate induces the assembly of cytoplasmic stress granules

Xue

Gao

et al. 2016

FEBS Letters

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Edited by Quan ChenMalonate, a classic inhibitor of respiratory electron transport chain, induces mitochondrial stress. Stress granules (SGs) are a kind of dynamic foci structure during stress. The study on the connection of mitochondrial stress and SG assembly is still limited. Here, we demonstrated that malonate treatment leads to SG formation and translation inhibition, apart from mitochondrial stress, including enhanced ROS formation, reduced mitochondrial Dw m and ATP level. The phosphorylation levels of eIF2a and 4EBP1 protein were affected upon mitochondrial dysfunction. However, knockdown of 4EBP1 affected SG formation, rather than eIF2a. In addition, an increase of ATP level under mitochondrial stress enhanced malonate-induced SG aggregation. Overall, malonate stimulation triggers mitochondrial stress and induces the assembly of non-canonical cellular SGs via 4EBP1 pathway.

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mRNPs meet stress granules

Sheinberger

Shav‐Tal

2017

FEBS Letters

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Edited by Wilhelm JustStress granules are cytoplasmic structures that form in response to a variety of cellular stresses. They contain mRNAs and many proteins including numerous types of RNA-binding proteins, and have been studied in connection to major cellular events such as protein synthesis as well as disease. Despite the well-known fact that stress granules encapsulate mRNPs (mRNA-protein complexes), much of the research has naturally focused on the protein components of stress granules. The specific details of mRNP entry into and exit from stress granules and the functional reasons for these dynamics are not fully understood. Here, we review studies that have concentrated on the aspects of mRNP accumulation in stress granules and produced quantitative data concerning mRNP/stress granule interactions.

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Stress granules, P-bodies and cancer

Cited by 351 publications

References 171 publications

Evidence That G-quadruplex DNA Accumulates in the Cytoplasm and Participates in Stress Granule Assembly in Response to Oxidative Stress

Evidence That G-quadruplex DNA Accumulates in the Cytoplasm and Participates in Stress Granule Assembly in Response to Oxidative Stress

Malonate induces the assembly of cytoplasmic stress granules

mRNPs meet stress granules

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