Stress granules are shock absorbers that prevent excessive innate immune responses to dsRNA
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA727598 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14436564_1.fastq.gz | Fastqsanger.gz | |||
| SRR14436564_2.fastq.gz | Fastqsanger.gz | |||
| SRR14436565_1.fastq.gz | Fastqsanger.gz | |||
| SRR14436565_2.fastq.gz | Fastqsanger.gz | |||
| SRR14436566_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 51 |
Similar Datasets
Project description:Proper defense against microbial infection depends on the controlled activation of the immune system. This is particularly important for the innate immune receptors that recognize viral double-stranded RNA (dsRNA) and initiate antiviral immune responses with the potential of triggering systemic inflammation and immunopathology. How the functions of the dsRNA receptors and their downstream effector molecules are coordinately regulated to avoid excessive immune response is poorly understood. We here demonstrate that stress granules (SGs), biomolecular condensates that form in response to various stresses including viral dsRNA, play key roles in regulating dsRNA-triggered immune response. Upon dsRNA stimulation, SGs recruit many innate immune molecules, including RIG-I-like receptors (RLRs), protein kinase R (PKR) and oligoadenylate synthases (OASes), target these molecules and dsRNA for autophagy and limit their functions through sequestration. In the absence of SGs, dsRNA stimulation results in hyperactivation of inflammatory signaling pathways, global translational arrest and bulk RNA degradation, altogether compromising the cellular capacity to restore homeostasis and triggering cell death. In contrast to most dsRNA-induced immune signaling pathways that are hyperactivated in the absence of SGs, a sub-branch of the RLR pathway (IRF3-dependent type I interferon signaling) shows time-dependent changes, where the initial spike in signaling is followed by a significant drop due to increased caspase-dependent negative feedback regulation. This highlights the role of SGs in regulating the delicate balance between the type I interferon pathway and cell death. Altogether, our data suggest that cells utilize SGs as shock absorbers to moderate antiviral innate immune response, thereby allowing cells to guard against its own immune system as well as viruses.
2021-05-06 | GSE173953 | GEO
Project description:Proper defense against microbial infection depends on the controlled activation of the immune system. This is particularly important for the RIG-I-like receptors (RLRs), which recognize viral dsRNA and initiate antiviral innate immune responses with the potential of triggering systemic inflammation and immunopathology. Here, we show that stress granules (SGs), molecular condensates that form in response to various stresses including viral dsRNA, play key roles in the controlled activation of RLR signaling. Without the SG nucleators G3BP1/2 and UBAP2L, dsRNA triggers excessive inflammation and immune-mediated apoptosis. In addition to exogenous dsRNA, host-derived dsRNA generated in response to ADAR1 deficiency is also controlled by SG biology. Intriguingly, SGs can function beyond immune control by suppressing viral replication independently of the RLR pathway. These observations thus highlight the multi-functional nature of SGs as cellular "shock absorbers" that converge on protecting cell homeostasis by dampening both toxic immune response and viral replication.
| S-EPMC10170497 | biostudies-literature
Project description:RNA in Trypanosoma brucei heat shock granules
| PRJEB12996 | ENA
Project description:Cell division ensures that both genetic information and non-genetic contents are inherited by daughter cells. Whereas considerable detail has been learned about the processing of intact or damaged DNA during the cell cycle (Branzei & Foiani, 2008; Klaasen et al., 2022),(Bakhoum & Cantley, 2018),(Hustedt & Durocher, 2016), how daughter cells deal with other forms of inherited damage is unknown. Here we identified a special kind of cytoplasmic granules responsible for the compartmentalisation of parental RNA damage. We found that ultraviolet (UV)-induced RNA, but not DNA, damage triggered assembly of this unique type of granules characterized by the presence of RNA helicase DHX9. By developing a novel methodology, FANCI, we discovered that DHX9 granules are enriched in damaged intron RNA and pre-mRNA-binding proteins, which is in contrast to other classical stress granules (SGs) that are composed of mature mRNA. Intron damage impeded proper splicing and intron decay, and induced generation of circRNA and dsRNA in the granules. Moreover, we showed that intron damage induced DHX9 granules assembled specifically in postmitotic daughter cells and triggered a cellular dsRNA immune response. Condensation with dsRNA is crucial for DHX9 localization to the granules and the modulation of dsRNA in these granules by DHX9 was crucial for daughter cell survival. Our observations revealed that DHX9 granules constitute a dedicated non-membrane-bound cytoplasmic compartment that protects daughter cells from parental damaged RNA.
2023-11-11 | GSE218180 | GEO
Project description:We observed that heat shock of Caenorhabditis elegans leads to the formation of nuclear double-stranded RNA (dsRNA) foci, detectable with a dsRNA-specific monoclonal antibody. These foci significantly overlap with nuclear HSF-1 granules. To investigate the molecular mechanism(s) underlying dsRNA foci formation, we used RNA-seq to globally characterize total RNA and immunoprecipitated dsRNA from control and heat-shocked worms. We find antisense transcripts are generally increased after heat shock, and a subset of both sense and antisense transcripts enriched in the dsRNA pool by heat shock overlap with dsRNA transcripts enriched by deletion of tdp-1, which encodes the C. elegans ortholog of TDP-43. Interestingly, transcripts involved in translation are over-represented in the dsRNAs induced by either heat shock or deletion of tdp-1. Also enriched in the dsRNA transcripts are sequences downstream of annotated genes (DoGs), which we globally quantified with a new algorithm. To validate these observations, we used fluorescence in situ hypridization (FISH) to confirm both antisense and downstream of gene transcription for eif-3.B, one of the affected loci we identified.
2018-10-09 | GSE120949 | GEO
Project description:T bruce were heat shocked for 1 h at 41C then granules were prepared as per Fritz et al. 2015. After spinning down cytoskeletons with trapped contents and lysing them we sequenced the supernatant (trapped RNA) and pellet (granule) fractions. Input total RNA is included for comparison.
2016-06-13 | E-MTAB-4557 | biostudies-arrayexpress
Project description:BUB1 is a nuclear serine/threonine protein kinase and a vital spindle assembly checkpoint (SAC) complex member responsible for proper chromosome segregation before mitosis. Here we report that BUB1 plays an unexpected cytoplasmic role in restraining DNA damage-induced accumulation of cytoplasmic dsRNA and ensuing immune response. We showed that tumors deficient in BUB1 were sensitive to radiotherapy in a CD8+T-cell-dependent manner. Furthermore, we discovered increased immune cell infiltration accompanied by elevated type I interferon production from irradiated BUB1-deficient cells, caused by enhanced cytoplasmic dsRNA accumulation and activation of the MDA5/MAVS/IRF7 dsRNA-sensing pathway. Mechanistically, we discovered that after exposure to ionizing radiation, BUB1 underwent a robust nucleus-to-cytoplasm migration, where it bound and phosphorylated the polyA-binding protein PABPC1, which was degraded together with its associated mRNAs stored in the stress granules, thereby preventing dsRNA accumulation and activation of the innate immune response. Our study, therefore, reveals a novel biological role for BUB1 in suppressing DNA-damage-induced cytoplasmic dsRNA accumulation/viral mimicry and provides a rationale for inhibiting BUB1 to enhance cytotoxic cancer therapy immunologically.
2025-10-18 | GSE246123 | GEO
Project description:BUB1 is a nuclear serine/threonine protein kinase and a vital spindle assembly checkpoint (SAC) complex member responsible for proper chromosome segregation before mitosis. Here we report that BUB1 plays an unexpected cytoplasmic role in restraining DNA damage-induced accumulation of cytoplasmic dsRNA and ensuing immune response. We showed that tumors deficient in BUB1 were sensitive to radiotherapy in a CD8+T-cell-dependent manner. Furthermore, we discovered increased immune cell infiltration accompanied by elevated type I interferon production from irradiated BUB1-deficient cells, caused by enhanced cytoplasmic dsRNA accumulation and activation of the MDA5/MAVS/IRF7 dsRNA-sensing pathway. Mechanistically, we discovered that after exposure to ionizing radiation, BUB1 underwent a robust nucleus-to-cytoplasm migration, where it bound and phosphorylated the polyA-binding protein PABPC1, which was degraded together with its associated mRNAs stored in the stress granules, thereby preventing dsRNA accumulation and activation of the innate immune response. Our study, therefore, reveals a novel biological role for BUB1 in suppressing DNA-damage-induced cytoplasmic dsRNA accumulation/viral mimicry and provides a rationale for inhibiting BUB1 to enhance cytotoxic cancer therapy immunologically.
2025-10-18 | GSE246124 | GEO
Project description:eIF1 discriminates against suboptimal initiation sites to prevent excessive uORF translation genome-wide
| PRJNA576487 | ENA
Project description:P granules in C. elegans are required for fertility and function to maintain germ cell identity and pluripotency. Sterility in the absence of P granules is often accompanied by the mis-expression of soma-specific proteins and the initiation of somatic differentiation in germ cells. To investigate whether this is caused by the accumulation of somatic transcripts, we performed mRNA-seq on dissected germlines with and without P granules. Strikingly, we found that somatic transcripts do not increase in the young adult germline when P granules are impaired. Instead, we found that impairing P granules causes sperm-specific mRNAs to become highly overexpressed. This includes the accumulation of major sperm protein (MSP) transcripts in germ cells, a phenotype that is suppressed by feminization of the germline. A core component of P granules, the endo-siRNA-binding Argonaute protein CSR-1, has recently been ascribed with the ability to license transcripts for germline expression. However, impairing CSR-1 has very little effect on the accumulation of its mRNA targets. Instead, we found that CSR-1 functions with P granules to prevent MSP and sperm-specific mRNAs from being transcribed in the hermaphrodite germline. These findings suggest that P granules protect germline integrity through two different mechanisms, by 1) preventing the inappropriate expression of somatic proteins at the level of translational regulation, and by 2) functioning with CSR-1 to limit the domain of sperm-specific expression at the level of transcription. Four biological replicates of each condition (empty vector control, P granule RNAi, and CSR-1 RNAi germlines) were collected for total RNA.
2015-05-20 | E-GEOD-67954 | biostudies-arrayexpress