Metazoan stress granule assembly is mediated by P-eIF2α-dependent and -independent mechanisms

Farny, Natalie G.; Kedersha, Nancy; Silver, Pamela A.

doi:10.1261/rna.1684009

Cited by 122 publications

(131 citation statements)

References 24 publications

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“…To confirm the association of Dnmt2 with stress-related subcellular compartments, we costained heatshocked S2 cells for Dnmt2-EGFP and fragile X mental retardation 1 (FMR1), a ubiquitious RNA-binding protein that relocalizes to stress granules in Drosophila (Farny et al 2009). The results showed that part of the Dnmt2-EGFP signal clearly colocalized with FMR1 loci (Fig.…”

Section: Resultsmentioning

confidence: 99%

RNA methylation by Dnmt2 protects transfer RNAs against stress-induced cleavage

Schaefer¹,

Pollex²,

Hanna³

et al. 2010

Genes Dev.

634

682

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Dnmt2 proteins are the most conserved members of the DNA methyltransferase enzyme family, but their substrate specificity and biological functions have been a subject of controversy. We show here that, in addition to tRNA Asp-GTC , tRNA Val-AAC and tRNA Gly-GCC are also methylated by Dnmt2. Drosophila Dnmt2 mutants showed reduced viability under stress conditions, and Dnmt2 relocalized to stress granules following heat shock. Strikingly, stress-induced cleavage of tRNAs was Dnmt2-dependent, and Dnmt2-mediated methylation protected tRNAs against ribonuclease cleavage. These results uncover a novel biological function of Dnmt2-mediated tRNA methylation, and suggest a role for Dnmt2 enzymes during the biogenesis of tRNA-derived small RNAs.Supplemental material is available at http://www.genesdev.org.

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Section: Resultsmentioning

confidence: 99%

RNA methylation by Dnmt2 protects transfer RNAs against stress-induced cleavage

Schaefer¹,

Pollex²,

Hanna³

et al. 2010

Genes Dev.

634

682

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show abstract

“…Ars and Pur elicit the formation of SG by distinct mechanisms. For example, Pur induces SG by disassembling polysomes whereas Ars induces SGs by eliciting eIF2 phosphorylation to result in a block to the recycling of the translation ternary complex (Farny et al, 2009;Kedersha et al, 2000). Because HIV-1 expression did not promote the phosphorylation of eIF2 in basal conditions, nor did it impair Ars-induced eIF2 phosphorylation (Fig.…”

Section: Discussionmentioning

confidence: 96%

Novel Staufen1 ribonucleoproteins prevent formation of stress granules but favour encapsidation of HIV-1 genomic RNA

Abrahamyan

Chatel‐Chaix

Ajamian

et al. 2010

Journal of Cell Science

116

191

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SummaryHuman immunodeficiency virus type 1 (HIV-1) Gag selects for and mediates genomic RNA (vRNA) encapsidation into progeny virus particles. The host protein, Staufen1 interacts directly with Gag and is found in ribonucleoprotein (RNP) complexes containing vRNA, which provides evidence that Staufen1 plays a role in vRNA selection and encapsidation. In this work, we show that Staufen1, vRNA and Gag are found in the same RNP complex. These cellular and viral factors also colocalize in cells and constitute novel Staufen1 RNPs (SHRNPs) whose assembly is strictly dependent on HIV-1 expression. SHRNPs are distinct from stress granules and processing bodies, are preferentially formed during oxidative stress and are found to be in equilibrium with translating polysomes. Moreover, SHRNPs are stable, and the association between Staufen1 and vRNA was found to be evident in these and other types of RNPs. We demonstrate that following Staufen1 depletion, apparent supraphysiologic-sized SHRNP foci are formed in the cytoplasm and in which Gag, vRNA and the residual Staufen1 accumulate. The depletion of Staufen1 resulted in reduced Gag levels and deregulated the assembly of newly synthesized virions, which were found to contain several-fold increases in vRNA, Staufen1 and other cellular proteins. This work provides new evidence that Staufen1-containing HIV-1 RNPs preferentially form over other cellular silencing foci and are involved in assembly, localization and encapsidation of vRNA.

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“…2009; Buchan and Parker 2009;Farny et al 2009), whereas stalling mRNAs in the elongation step of translation inhibits SG formation . We therefore tested whether 59TOP mRNAs accumulate in SGs upon amino acid starvation.…”

Section: Tia-1 and Tiar Show Starvation-stimulated Association With 5mentioning

confidence: 99%

Translational coregulation of 5′TOP mRNAs by TIA-1 and TIAR

Damgaard¹,

2011

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The response of cells to changes in their environment often requires coregulation of gene networks, but little is known about how this can occur at the post-transcriptional level. An important example of post-transcriptional coregulation is the selective translational regulation in response to growth conditions of mammalian mRNAs that encode protein biosynthesis factors and contain hallmark 59-terminal oligopyrimidine tracts (59TOP). However, the responsible trans-factors and the mechanism by which they coregulate 59TOP mRNAs have remained elusive. Here we identify stress granule-associated TIA-1 and TIAR proteins as key factors in human 59TOP mRNA regulation, which upon amino acid starvation assemble onto the 59 end of 59TOP mRNAs and arrest translation at the initiation step, as evidenced by TIA-1/TIAR-dependent 59TOP mRNA translation repression, polysome release, and accumulation in stress granules. This requires starvation-mediated activation of the GCN2 (general control nonderepressible 2) kinase and inactivation of the mTOR (mammalian target of rapamycin) signaling pathway. Our findings provide a mechanistic explanation to the long-standing question of how the network of 59TOP mRNAs are coregulated according to amino acid availability, thereby allowing redirection of limited resources to mount a nutrient deprivation response. This presents a fundamental example of how a group of mRNAs can be translationally coregulated in response to changes in the cellular environment.

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Metazoan stress granule assembly is mediated by P-eIF2α-dependent and -independent mechanisms

Cited by 122 publications

References 24 publications

RNA methylation by Dnmt2 protects transfer RNAs against stress-induced cleavage

RNA methylation by Dnmt2 protects transfer RNAs against stress-induced cleavage

Novel Staufen1 ribonucleoproteins prevent formation of stress granules but favour encapsidation of HIV-1 genomic RNA

Translational coregulation of 5′TOP mRNAs by TIA-1 and TIAR

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