The <i>C. elegans</i> TIA‐1/TIAR homolog TIAR‐1 is required to induce germ cell apoptosis

Giovanni, Silva-García Carlos; Rosa, Estela Navarro

doi:10.1002/dvg.22418

Cited by 17 publications

(19 citation statements)

References 57 publications

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“…S6). We could not detect expression of GFP fusions in germline due to silencing of transgenes in this tissue [74] but previous studies have shown the expression of TIAR-1 [33], [75] and TIAR-2 [32] in germ granules.…”

Section: Resultsmentioning

confidence: 95%

“…We assume that deletion of TIAR-1 affects only specific functions of SGs related to oxidative stress response and not to heat-shock, although it localizes to SGs formed under both conditions. Alternatively, since TIAR-1 is required to induce germ cell apoptosis under various stresses [75], the increased resistance of tiar-1 mutants to heat-shock might be related to the systemic stress response that is observed in several DNA-damage checkpoint mutants affecting programmed cell death in germline [77], [78]. In sharp contrast to tiar-1 worms, tiar-2 or tiar-3 mutants had increased mortality under heat and osmotic stress but survived as N2 under oxidative or UV-irradiation stress (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Diverse Functions of mRNA Metabolism Factors in Stress Defense and Aging of Caenorhabditis elegans

et al. 2014

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Processing bodies (PBs) and stress granules (SGs) are related, cytoplasmic RNA-protein complexes that contribute to post-transcriptional gene regulation in all eukaryotic cells. Both structures contain translationally repressed mRNAs and several proteins involved in silencing, stabilization or degradation of mRNAs, especially under environmental stress. Here, we monitored the dynamic formation of PBs and SGs, in somatic cells of adult worms, using fluorescently tagged protein markers of each complex. Both complexes were accumulated in response to various stress conditions, but distinct modes of SG formation were induced, depending on the insult. We also observed an age-dependent accumulation of PBs but not of SGs. We further showed that direct alterations in PB-related genes can influence aging and normal stress responses, beyond their developmental role. In addition, disruption of SG-related genes had diverse effects on development, fertility, lifespan and stress resistance of worms. Our work therefore underlines the important roles of mRNA metabolism factors in several vital cellular processes and provides insight into their diverse functions in a multicellular organism.

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Section: Resultsmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 99%

Diverse Functions of mRNA Metabolism Factors in Stress Defense and Aging of Caenorhabditis elegans

et al. 2014

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“…The fertility assay and embryonic lethality were done as previously described [ 32 ]. N2 and mai-2 mutants were grown at 20°C and were individually selected as L4 larvae and then transferred to new plate every 24 h over the course of 4 days.…”

Section: Methodsmentioning

confidence: 99%

“…We selected L4 animals of each strain and approximately 24 h later we mounted on slides using 2% agarose pads; the cell corpses were then visualized by fluorescence microscopy using a Nikon Eclipse E600 microscope equipped with an AxioCam MRc camera (Zeiss). For stress conditions, such as starvation, oxidative stress, heat shock and UV irradiation (DNA damage) we performed experiments as previously described [ 32 , 42 ]. To quantify apoptosis in the soma, synchronized L1 animals of N2, mai-2(xm18) and mai-2(xm19) strains grown at 20°C were fed ced-1 dsRNA until they had offspring as previously described [ 42 ].…”

Section: Methodsmentioning

confidence: 99%

Caenorhabditis elegans ATPase inhibitor factor 1 (IF1) MAI-2 preserves the mitochondrial membrane potential (Δψm) and is important to induce germ cell apoptosis

et al. 2017

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When the electrochemical proton gradient is disrupted in the mitochondria, IF1 (Inhibitor Factor-1) inhibits the reverse hydrolytic activity of the F1Fo-ATP synthase, thereby allowing cells to conserve ATP at the expense of losing the mitochondrial membrane potential (Δψm). The function of IF1 has been studied mainly in different cell lines, but these studies have generated contrasting results, which have not been helpful to understand the real role of this protein in a whole organism. In this work, we studied IF1 function in Caenorhabditis elegans to understand IF1´s role in vivo. C. elegans has two inhibitor proteins of the F1Fo-ATPase, MAI-1 and MAI-2. To determine their protein localization in C. elegans, we generated translational reporters and found that MAI-2 is expressed ubiquitously in the mitochondria; conversely, MAI-1 was found in the cytoplasm and nuclei of certain tissues. By CRISPR/Cas9 genome editing, we generated mai-2 mutant alleles. Here, we showed that mai-2 mutant animals have normal progeny, embryonic development and lifespan. Contrasting with the results previously obtained in cell lines, we found no evident defects in the mitochondrial network, dimer/monomer ATP synthase ratio, ATP concentration or respiration. Our results suggest that some of the roles previously attributed to IF1 in cell lines could not reflect the function of this protein in a whole organism and could be attributed to specific cell lines or methods used to silence, knockout or overexpress this protein. However, we did observe that animals lacking IF1 had an enhanced Δψm and lower physiological germ cell apoptosis. Importantly, we found that mai-2 mutant animals must be under stress to observe the role of IF1. Accordingly, we observed that mai-2 mutant animals were more sensitive to heat shock, oxidative stress and electron transport chain blockade. Furthermore, we observed that IF1 is important to induce germ cell apoptosis under certain types of stress. Here, we propose that MAI-2 might play a role in apoptosis by regulating Δψm. Additionally, we suggest that IF1 function is mainly observed under stress and that, under physiological conditions, this protein does not play an essential role.

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“…C. elegans has three TIA-1/TIAR homologs: tiar-1 , -2 , and -3 (WormBase release WS204). Among the three homologs, tiar-1 is uniquely required for the induction of germ cell apoptosis under several stressful conditions ( Silva-García and Navarro 2013 ). tiar-1 mutant animals exhibit reduced longevity and small brood sizes and are hypersensitive to oxidative and UV stress ( Silva-García and Navarro 2013 ; Rousakis et al 2014 ).…”

mentioning

confidence: 99%

The Stress Granule RNA-Binding Protein TIAR-1 Protects Female Germ Cells from Heat Shock inCaenorhabditis elegans

Huelgas-Morales

Silva-García

Salinas

et al. 2016

G3 Genes|Genomes|Genetics

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In response to stressful conditions, eukaryotic cells launch an arsenal of regulatory programs to protect the proteome. One major protective response involves the arrest of protein translation and the formation of stress granules, cytoplasmic ribonucleoprotein complexes containing the conserved RNA-binding proteins TIA-1 and TIAR. The stress granule response is thought to preserve mRNA for translation when conditions improve. For cells of the germline—the immortal cell lineage required for sexual reproduction—protection from stress is critically important for perpetuation of the species, yet how stress granule regulatory mechanisms are deployed in animal reproduction is incompletely understood. Here, we show that the stress granule protein TIAR-1 protects the Caenorhabditis elegans germline from the adverse effects of heat shock. Animals containing strong loss-of-function mutations in tiar-1 exhibit significantly reduced fertility compared to the wild type following heat shock. Analysis of a heat-shock protein promoter indicates that tiar-1 mutants display an impaired heat-shock response. We observed that TIAR-1 was associated with granules in the gonad core and oocytes during several stressful conditions. Both gonad core and oocyte granules are dynamic structures that depend on translation; protein synthesis inhibitors altered their formation. Nonetheless, tiar-1 was required for the formation of gonad core granules only. Interestingly, the gonad core granules did not seem to be needed for the germ cells to develop viable embryos after heat shock. This suggests that TIAR-1 is able to protect the germline from heat stress independently of these structures.

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The C. elegans TIA‐1/TIAR homolog TIAR‐1 is required to induce germ cell apoptosis

Cited by 17 publications

References 57 publications

Diverse Functions of mRNA Metabolism Factors in Stress Defense and Aging of Caenorhabditis elegans

Diverse Functions of mRNA Metabolism Factors in Stress Defense and Aging of Caenorhabditis elegans

Caenorhabditis elegans ATPase inhibitor factor 1 (IF1) MAI-2 preserves the mitochondrial membrane potential (Δψm) and is important to induce germ cell apoptosis

The Stress Granule RNA-Binding Protein TIAR-1 Protects Female Germ Cells from Heat Shock inCaenorhabditis elegans

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