Suppression of the mRNA export pathway dampens viral mimicry response and promotes tumor immune evasion [RIP-Seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1137904 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR29891801_1.fastq.gz | Fastqsanger.gz | |||
| SRR29891801_2.fastq.gz | Fastqsanger.gz | |||
| SRR29891803_1.fastq.gz | Fastqsanger.gz | |||
| SRR29891803_2.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 21 |
Similar Datasets
Project description:Transcriptional induction of retroelement transcripts through therapeutic interventions elevates cytosolic double-stranded RNA (dsRNA) levels to trigger viral mimicry response and anti-tumor immunity. Therapeutic interventions that transcriptionally induce retroelement transcripts lead to elevated levels of cytosolic double-stranded RNA (dsRNA), thereby triggering a viral mimicry response and enhancing anti-tumor immunity. Despite the promising implications, clinical studies have revealed substantial variations in the therapeutic induction of viral mimicry response in different cancer patients, with the underlying mechanisms remaining largely elusive. In this study, we illuminate the pivotal role of the mRNA export pathway in viral mimicry response and anti-tumor T cell immunity. Notably, epigenetic and posttranscriptional induction of cytosolic dsRNAs necessitates the mRNA export pathway to transport the nuclear-transcribed retroelement transcripts into the cytoplasm, which is posttranscriptionally suppressed by the RNA exosome in coactivator-associated arginine methyltransferase 1 (CARM1)-expressing tumor cells. Mechanistically, Carm1 restricts the nuclear export of retroelement transcripts through transcriptional elevation and posttranslational stabilization of the RNA exosome, which hydrolyzes the critical nuclear RNA export adaptor transcripts Ddx39a and Alyref. Collectively, our study underscores the vital importance of the mRNA export pathway in viral mimicry response and suggests that enhancing its activity through Carm1 or RNA exosome inhibition could reinforce therapy-induced viral mimicry response, thus holding the potential to overcome tumor immune escape and immunotherapy resistance.
2025-06-01 | GSE272658 | GEO
Project description:Suppression of the mRNA export pathway dampens viral mimicry response and promotes tumor immune evasion
| PRJNA1054582 | ENA
Project description:Transcriptional induction of retroelement transcripts through therapeutic interventions elevates cytosolic double-stranded RNA (dsRNA) levels to trigger viral mimicry response and anti-tumor immunity. Therapeutic interventions that transcriptionally induce retroelement transcripts lead to elevated levels of cytosolic double-stranded RNA (dsRNA), thereby triggering a viral mimicry response and enhancing anti-tumor immunity. Despite the promising implications, clinical studies have revealed substantial variations in the therapeutic induction of viral mimicry response in different cancer patients, with the underlying mechanisms remaining largely elusive. In this study, we illuminate the pivotal role of the mRNA export pathway in viral mimicry response and anti-tumor T cell immunity. Notably, epigenetic and posttranscriptional induction of cytosolic dsRNAs necessitates the mRNA export pathway to transport the nuclear-transcribed retroelement transcripts into the cytoplasm, which is posttranscriptionally suppressed by the RNA exosome in coactivator-associated arginine methyltransferase 1 (CARM1)-expressing tumor cells. Mechanistically, Carm1 restricts the nuclear export of retroelement transcripts through transcriptional elevation and posttranslational stabilization of the RNA exosome, which hydrolyzes the critical nuclear RNA export adaptor transcripts Ddx39a and Alyref. Collectively, our study underscores the vital importance of the mRNA export pathway in viral mimicry response and suggests that enhancing its activity through Carm1 or RNA exosome inhibition could reinforce therapy-induced viral mimicry response, thus holding the potential to overcome tumor immune escape and immunotherapy resistance.
2025-06-01 | GSE250588 | GEO
Project description:Transcriptional induction of retroelement transcripts through therapeutic interventions elevates cytosolic double-stranded RNA (dsRNA) levels to trigger viral mimicry response and anti-tumor immunity. Therapeutic interventions that transcriptionally induce retroelement transcripts lead to elevated levels of cytosolic double-stranded RNA (dsRNA), thereby triggering a viral mimicry response and enhancing anti-tumor immunity. Despite the promising implications, clinical studies have revealed substantial variations in the therapeutic induction of viral mimicry response in different cancer patients, with the underlying mechanisms remaining largely elusive. In this study, we illuminate the pivotal role of the mRNA export pathway in viral mimicry response and anti-tumor T cell immunity. Notably, epigenetic and posttranscriptional induction of cytosolic dsRNAs necessitates the mRNA export pathway to transport the nuclear-transcribed retroelement transcripts into the cytoplasm, which is posttranscriptionally suppressed by the RNA exosome in coactivator-associated arginine methyltransferase 1 (CARM1)-expressing tumor cells. Mechanistically, Carm1 restricts the nuclear export of retroelement transcripts through transcriptional elevation and posttranslational stabilization of the RNA exosome, which hydrolyzes the critical nuclear RNA export adaptor transcripts Ddx39a and Alyref. Collectively, our study underscores the vital importance of the mRNA export pathway in viral mimicry response and suggests that enhancing its activity through Carm1 or RNA exosome inhibition could reinforce therapy-induced viral mimicry response, thus holding the potential to overcome tumor immune escape and immunotherapy resistance.
2025-06-01 | GSE250590 | GEO
Project description:Suppression of the mRNA export pathway dampens viral mimicry response and promotes tumor immune evasion [RNA-seq]
| PRJNA1054587 | ENA
Project description:Suppression of the mRNA export pathway dampens viral mimicry response and promotes tumor immune evasion [ChIP-seq]
| PRJNA1054580 | ENA
Project description:Epigenetic therapies that alter DNA- and/or histone modifications facilitate transcription of immunogenic repetitive elements that cull cancer cells through ‘viral mimicry’ responses. Paradoxically, cancer-initiating events that include functional inactivation of canonical tumor suppressor proteins also facilitate transcription of repetitive elements. Contributions of repetitive element transcription towards cancer initiation, and the mechanisms by which cancer cells evade lethal viral mimicry responses during tumor initiation remain poorly understood. In this report, we characterize patient-derived premalignant lesions of the fallopian tube along with syngeneic mouse models of epithelial ovarian cancer to explore the earliest events of tumorigenesis following loss of the p53 tumor suppressor protein. We report that p53 loss disrupts constitutive heterochromatin to permit transcription of immunogenic repetitive elements capable of activating viral mimicry responses. While acute viral mimicry activation diminishes cell fitness, chronic viral mimicry activation following p53 loss promotes epigenetic reprogramming that increases tolerance of cytosolic nucleic acids and diminishes cellular immunogenicity as a pro-survival adaptation. This selection process we describe as ‘viral mimicry conditioning’ can be partially attenuated by the reverse transcriptase inhibitor 3TC to delay spontaneous tumorigenesis. Altogether, these results reveal that viral mimicry conditioning following p53 loss selects for diminished cell immunogenicity to promote immune evasion upon cancer initiation. Disruption of viral mimicry conditioning during cancer initiation may represent a pharmacological target for early cancer interception.
2024-12-10 | GSE216941 | GEO
Project description:Epigenetic therapies that alter DNA- and/or histone modifications facilitate transcription of immunogenic repetitive elements that cull cancer cells through ‘viral mimicry’ responses. Paradoxically, cancer-initiating events that include functional inactivation of canonical tumor suppressor proteins also facilitate transcription of repetitive elements. Contributions of repetitive element transcription towards cancer initiation, and the mechanisms by which cancer cells evade lethal viral mimicry responses during tumor initiation remain poorly understood. In this report, we characterize patient-derived premalignant lesions of the fallopian tube along with syngeneic mouse models of epithelial ovarian cancer to explore the earliest events of tumorigenesis following loss of the p53 tumor suppressor protein. We report that p53 loss disrupts constitutive heterochromatin to permit transcription of immunogenic repetitive elements capable of activating viral mimicry responses. While acute viral mimicry activation diminishes cell fitness, chronic viral mimicry activation following p53 loss promotes epigenetic reprogramming that increases tolerance of cytosolic nucleic acids and diminishes cellular immunogenicity as a pro-survival adaptation. This selection process we describe as ‘viral mimicry conditioning’ can be partially attenuated by the reverse transcriptase inhibitor 3TC to delay spontaneous tumorigenesis. Altogether, these results reveal that viral mimicry conditioning following p53 loss selects for diminished cell immunogenicity to promote immune evasion upon cancer initiation. Disruption of viral mimicry conditioning during cancer initiation may represent a pharmacological target for early cancer interception.
2024-12-10 | GSE216640 | GEO
Project description:Epigenetic therapies that alter DNA- and/or histone modifications facilitate transcription of immunogenic repetitive elements that cull cancer cells through ‘viral mimicry’ responses. Paradoxically, cancer-initiating events that include functional inactivation of canonical tumor suppressor proteins also facilitate transcription of repetitive elements. Contributions of repetitive element transcription towards cancer initiation, and the mechanisms by which cancer cells evade lethal viral mimicry responses during tumor initiation remain poorly understood. In this report, we characterize patient-derived premalignant lesions of the fallopian tube along with syngeneic mouse models of epithelial ovarian cancer to explore the earliest events of tumorigenesis following loss of the p53 tumor suppressor protein. We report that p53 loss disrupts constitutive heterochromatin to permit transcription of immunogenic repetitive elements capable of activating viral mimicry responses. While acute viral mimicry activation diminishes cell fitness, chronic viral mimicry activation following p53 loss promotes epigenetic reprogramming that increases tolerance of cytosolic nucleic acids and diminishes cellular immunogenicity as a pro-survival adaptation. This selection process we describe as ‘viral mimicry conditioning’ can be partially attenuated by the reverse transcriptase inhibitor 3TC to delay spontaneous tumorigenesis. Altogether, these results reveal that viral mimicry conditioning following p53 loss selects for diminished cell immunogenicity to promote immune evasion upon cancer initiation. Disruption of viral mimicry conditioning during cancer initiation may represent a pharmacological target for early cancer interception.
2024-12-10 | GSE216945 | GEO
Project description:Epigenetic therapies that alter DNA- and/or histone modifications facilitate transcription of immunogenic repetitive elements that cull cancer cells through ‘viral mimicry’ responses. Paradoxically, cancer-initiating events that include functional inactivation of canonical tumor suppressor proteins also facilitate transcription of repetitive elements. Contributions of repetitive element transcription towards cancer initiation, and the mechanisms by which cancer cells evade lethal viral mimicry responses during tumor initiation remain poorly understood. In this report, we characterize patient-derived premalignant lesions of the fallopian tube along with syngeneic mouse models of epithelial ovarian cancer to explore the earliest events of tumorigenesis following loss of the p53 tumor suppressor protein. We report that p53 loss disrupts constitutive heterochromatin to permit transcription of immunogenic repetitive elements capable of activating viral mimicry responses. While acute viral mimicry activation diminishes cell fitness, chronic viral mimicry activation following p53 loss promotes epigenetic reprogramming that increases tolerance of cytosolic nucleic acids and diminishes cellular immunogenicity as a pro-survival adaptation. This selection process we describe as ‘viral mimicry conditioning’ can be partially attenuated by the reverse transcriptase inhibitor 3TC to delay spontaneous tumorigenesis. Altogether, these results reveal that viral mimicry conditioning following p53 loss selects for diminished cell immunogenicity to promote immune evasion upon cancer initiation. Disruption of viral mimicry conditioning during cancer initiation may represent a pharmacological target for early cancer interception.
2024-03-26 | GSE216639 | GEO