DAZL is essential for stress granule formation implicated in germ cell survival upon heat stress

Kim, Byunghyuk; Cooke, Howard J.; Rhee, Kunsoo

doi:10.1242/dev.075846

Cited by 75 publications

(100 citation statements)

References 57 publications

(84 reference statements)

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“…Thus, the dynamic cycle of SG assembly/disassembly can be viewed as a strategy to cope with disruptions in translation caused by environmental stress. In keeping with this view, cells with impairments in SG assembly show decreased ability to survive exposure to stressful stimuli (1)(2)(3).…”

mentioning

confidence: 68%

The Herpes Simplex Virus 2 Virion-Associated Ribonuclease vhs Interferes with Stress Granule Formation

Finnen

Hay

Dauber

et al. 2014

J Virol

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In a previous study, it was observed that cells infected with herpes simplex virus 2 (HSV-2) failed to accumulate stress granules (SGs) in response to oxidative stress induced by arsenite treatment. As a follow-up to this observation, we demonstrate here that disruption of arsenite-induced SG formation by HSV-2 is mediated by a virion component. Through studies on SG formation in cells infected with HSV-2 strains carrying defective forms of UL41, the gene that encodes vhs, we identify vhs as a virion component required for this disruption. Cells infected with HSV-2 strains producing defective forms of vhs form SGs spontaneously late in infection. In addition to core SG components, these spontaneous SGs contain the viral immediate early protein ICP27 as well as the viral serine/threonine kinase Us3. As part of these studies, we reexamined the frameshift mutation known to reside within the UL41 gene of HSV-2 strain HG52. We demonstrate that this mutation is unstable and can rapidly revert to restore wild-type UL41 following low-multiplicity passaging. Identification of the involvement of virion-associated vhs in the disruption of SG formation will enable mechanistic studies on how HSV-2 is able to counteract antiviral stress responses early in infection. In addition, the ability of Us3 to localize to stress granules may indicate novel roles for this viral kinase in the regulation of translation. IMPORTANCEEukaryotic cells respond to stress by rapidly shutting down protein synthesis and storing mRNAs in cytoplasmic stress granules (SGs). Stoppages in protein synthesis are problematic for all viruses as they rely on host cell machinery to synthesize viral proteins. Thus, many viruses target SGs for disruption or modification. Infection by herpes simplex virus 2 (HSV-2) was previously observed to disrupt SG formation induced by oxidative stress. In this follow-up study, we identify virion host shutoff protein (vhs) as a viral protein involved in this disruption. The identification of a specific viral protein involved in disrupting SG formation is a key step toward understanding how HSV-2 interacts with these antiviral structures. Additionally, this understanding may provide insights into the biology of SGs that may find application in studies on human motor neuron degenerative diseases, like amyotrophic lateral sclerosis (ALS), which may arise as a result of dysregulation of SG formation.

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mentioning

confidence: 68%

The Herpes Simplex Virus 2 Virion-Associated Ribonuclease vhs Interferes with Stress Granule Formation

Finnen

Hay

Dauber

et al. 2014

J Virol

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“…In addition to these proteins, the ubiquitous category is highly enriched with the components of the spliceosome (SRSF9, SRSF2, U2AF1, HNRNPL) and proteasome (UBC, UBE2I, UBE2D3). Majority of the RBPs (60%) constituted tissue-specific category ( Figure 4C) and included heat response protein 12, HRSP12, known to be expressed in kidney and liver [60], DAZL -a germ cell specific RBP [61], member of the CELF family CELF3 that is highly expressed in brain [62], PUF60-poly-U binding splicing factor 60kDa, that was recently shown to be required for the splicing of a subset of tissue-specific splicing events which when deregulated in the absence of PUF60 affect the development of organs such as brain, heart, kidney and eye [63]. Analysis of the comparison of expression patterns of classical and non-classical RBPs in each of the 16 tissues revealed that in ~50% of the tissues, the expression of non-classical RBPs was significantly higher than the classical RBPs (p<0.05, Wilcoxon test) ( Figure 4D).…”

Section: Majority Of the Rbps Exhibit Tissue-specific Protein Expressmentioning

confidence: 99%

The human RBPome: From genes and proteins to human disease

Neelamraju

Hashemikhabir

Janga

2015

Journal of Proteomics

110

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“…In addition, other cellular proteins could be packed into stress granules, including Tudor Staphylococcal Nuclease (Tudor-SN, also known as SND1), adenosine deaminase acting on RNA 1 (ADAR1) (Weissbach and Scadden, 2012), DAZL (Kim et al, 2012), p90 ribosomal S6 kinase 2 (RSK2, also known as RPS6KA3), Ras homolog gene family member A and Rho-associated coiled-coil forming kinase 1 (RhoA and ROCK1) (Tsai and Wei, 2010), 2-oxoglutarate and Fe(II)-dependent oxygenase domain containing 1 (OGFOD1) (Wehner et al, 2010), melanoma differentiationassociated gene 5 (MDA5, also known as IFIH1) and retinoicacid-inducible gene I (RIG-I, also known as DDX58) (Langereis et al, 2013;Onomoto et al, 2012). When conditions that are suitable for translation are restored, the components of stress granules are dynamically released so that translation is rapidly resumed.…”

Section: Introductionmentioning

confidence: 99%

IPS-1 plays an essential role in stress granule formation induced by dsRNA through interacting with PKR and mediating its activation

Zhang

Xia

et al. 2014

Journal of Cell Science

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BSTRACTThe formation of cytoplasmic stress granules and the innate immune response are two distinct cellular stress responses. Our study investigated the involvement of four innate immune proteinsretinoic-acid-inducible gene I (RIG-I, also known as DDX58), melanoma differentiation-associated gene 5 (MDA5, also known as IFIH1), IFN-b promoter stimulator (IPS-1, also known as MAVS) and protein kinase regulated by dsRNA (PKR, also known as EIF2AK2) in the formation of stress granules. Knockdown of IPS-1 or PKR significantly decreased the formation of stress granules induced by double-stranded (ds)RNA. IPS-1 depletion markedly attenuated the phosphorylation of PKR and eIF2a that was triggered by dsRNA, and IPS-1 facilitated the in vitro autophosphorylation of PKR. In IPS-1-depleted cells, the dsRNAmediated dimerization of PKR through its dsRNA-binding domains was significantly abrogated, suggesting that IPS-1 might be involved in PKR dimerization. By co-immunoprecipitation and pulldown assays, our data demonstrate that IPS-1 directly binds to PKR through the IPS-1 caspase activation and recruitment domain (CARD), suggesting that the effect of IPS-1 on the formation of stress granules might be exerted through interacting with PKR and mediating its activation. PKR was recruited into stress granules upon activation, whereas the majority of IPS-1 protein formed clusters on mitochondrial membranes. Our work provides the first evidence that the innate signaling molecule IPS-1 plays an essential role in stress granule formation.

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DAZL is essential for stress granule formation implicated in germ cell survival upon heat stress

Cited by 75 publications

References 57 publications

The Herpes Simplex Virus 2 Virion-Associated Ribonuclease vhs Interferes with Stress Granule Formation

The Herpes Simplex Virus 2 Virion-Associated Ribonuclease vhs Interferes with Stress Granule Formation

The human RBPome: From genes and proteins to human disease

IPS-1 plays an essential role in stress granule formation induced by dsRNA through interacting with PKR and mediating its activation

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