Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA389742 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:p62 sustains a protumorigenic gene signature in melanoma opposing mRNA-dependent decay [UACC62_6days]
| PRJNA389744 | ENA
Project description:p62 sustains a protumorigenic gene signature in melanoma opposing mRNA-dependent decay [UACC62_3days]
| PRJNA389745 | ENA
Project description:p62 sustains a protumorigenic gene signature in melanoma opposing mRNA-dependent decay [SKMEL_3days]
| PRJNA389743 | ENA
Project description:p62 sustains a protumorigenic gene signature in melanoma opposing mRNA-dependent decay
| PRJNA389739 | ENA
Project description:mRNA decay factors regulate mRNA turnover by recruiting non-translating mRNAs and targeting them for degradation, yet it remains poorly understood how mRNA decay factors function in vivo to regulate specific cellular processes. Here we show that mRNA decay factors form cytoplasmic puncta in C. elegans neurons and have opposing roles in axon maintenance and regrowth. While the decapping enzymes DCAP-1/DCP1 and DCAP-2/DCP2 regulate developmental axon guidance and promote axon regrowth upon injury, the translational repressors CAR-1/LSM14 and CGH-1/DDX6 regulate axon maintenance and inhibit axon regrowth in adult animals. We identified mRNA targets of CAR-1 in neurons and found that the mitochondrial calcium uptake regulator micu-1 is repressed by CAR-1. We show that axon injury triggers a transient mitochondrial calcium influx via the MCU-1 uniporter that is more sustained in car-1 loss of function mutants. The enhanced axon regrowth and defective axon maintenance of car-1 mutants are dependent on MICU-1 function. Our results uncover specific roles for mRNA decay regulators in neurons and reveal a novel pathway that controls axon regrowth through mitochondrial calcium uptake.
2020-01-23 | GSE124714 | GEO
Project description:mRNA abundances are regulated by the opposing forces of transcription and decay, and yet how decay contributes to mRNA abundance regulation is largely unexplored. We addressed this question using genome-wide data on mRNA rates of abundance change, half-lives, and transcription rates of leaf cells responding to a transdifferentiation stimulusulus. Half-life regulation was common (22% of mRNAs underwent changes in half-life), but RNA abundance regulation by decay alone or by decay that supported transcriptional regulation was rare. Instead, most altered RNA half-lives opposed changes in transcription. Oppositionally regulated mRNAs were characterized by large changes in transcription and decay rates yet changes in mRNA abundances were either modest or undetectable, suggestive of RNA buffering. Oppositionally-regulated and buffered RNAs showed very similar dynamics, suggesting use of a common mechanism. The strongest contributions of RNA decay to RNA abundance regulation was in synergistically regulated transcripts, where rate changes in decay and transcription rates worked together to change RNA abundances.
2024-10-11 | GSE278544 | GEO
Project description:mRNA abundances are regulated by the opposing forces of transcription and decay, and yet how decay contributes to mRNA abundance regulation is largely unexplored. We addressed this question using genome-wide data on mRNA rates of abundance change, half-lives, and transcription rates of leaf cells responding to a transdifferentiation stimulusulus. Half-life regulation was common (22% of mRNAs underwent changes in half-life), but RNA abundance regulation by decay alone or by decay that supported transcriptional regulation was rare. Instead, most altered RNA half-lives opposed changes in transcription. Oppositionally regulated mRNAs were characterized by large changes in transcription and decay rates yet changes in mRNA abundances were either modest or undetectable, suggestive of RNA buffering. Oppositionally-regulated and buffered RNAs showed very similar dynamics, suggesting use of a common mechanism. The strongest contributions of RNA decay to RNA abundance regulation was in synergistically regulated transcripts, where rate changes in decay and transcription rates worked together to change RNA abundances.
2024-10-11 | GSE278543 | GEO
Project description:p62/SQSTM1 was identified as a modulator of metastatic genes selectively enriched in melanoma in autophagy independent manner. iTRAQ quantitative proteomic approach was performed in melanoma cell lines (SK-Mel-103 and UACC-62) deficient for p62 to identify downstream effectors of p62. Similar studies were performed for ATG5, a core component of autophagy, as a reference for autophagy-associated changes in protein abundance. Additionally, melanoma cells were subjected to affinity purification (AP-MS) to identify the interactors of p62. Overall, these studies underscore a novel unexpected role of p62 regulating the stability of prometastatic factors via the interaction with RNA Binding Proteins, thus leading to the inhibition of protein translation.
2022-02-28 | PXD006650 | Pride
Project description:p62/SQSTM1 was identified as a modulator of metastatic genes selectively enriched in melanoma in autophagy independent manner. iTRAQ quantitative proteomic approach was performed in melanoma cell lines (SK-Mel-103 and UACC-62) deficient for p62 to identify downstream effectors of p62. Similar studies were performed for ATG5, a core component of autophagy, as a reference for autophagy-associated changes in protein abundance. Additionally, melanoma cells were subjected to affinity purification (AP-MS) to identify the interactors of p62. Overall, these studies underscore a novel unexpected role of p62 regulating the stability of prometastatic factors via the interaction with RNA Binding Proteins, thus leading to the inhibition of protein translation.
2021-10-29 | PXD007000 | Pride
Project description:The inflammasome sensor NLRP1 is mainly expressed by epithelial cells including keratinocytes of human skin. Germline gain-of-function mutations in NLRP1 cause inflammatory skin syndromes and predispose patients to the development of cutaneous squamous cell carcinomas (cSCCs), a major type of skin cancer originating from keratinocytes. However, expression of NLRP1 is strongly reduced in cSCCs suggesting a complex role of the NLRP1 inflammasome in the development of this type of skin cancer. Suppression of NLRP1 expression in SCC cells is partially caused by an increase in p62 (SQSTM1), a cargo receptor for autophagy-dependent protein degradation. p62 is upregulated in numerous types of cancer and plays key roles in tumor development by activating different pathways. Here, we characterized the molecular mechanisms underlying suppression of NLRP1 expression by p62 in cSCCs. In SCC cells, NLRP1 activation is rescued by a knockdown or knockout of p62 mRNA and, consequently, protein expression, rather than by a knockout of p62 protein expression only. As these experiments suggest a regulation of NLRP1 by the p62 mRNA, we characterized p62 mRNA-regulated gene expression in SCC cells through RNA sequencing. In addition to mRNAs, we identified several differentially regulated microRNAs (miRs), including miR-34a-5p. These short non-coding RNAs regulate the stability or translation of mRNAs in a dynamic manner and a single miR can target multiple mRNAs. miR-34a-5p is an established tumor suppressor in different types of cancer and its expression is also downregulated in cSCCs. Although miR-34a-5p seems to bind neither p62 nor NLRP1 mRNA directly, it increases NLRP1 expression, most likely through a complex mechanism at the RNA level. In summary, our findings revealed a novel pathway regulating suppression of the inflammasome sensor NLRP1 in SCC cells by p62, which occurs at the mRNA level and is mediated by miRs, including the tumor suppressive miR-34a-5p. p62 mRNA, but not protein, regulates expression of other mRNAs and miRNAs. Differential expression analysis of RNA-seq data from SCC12 cells with a protein (p62.1) or mRNA (p62.2K) knockout, and control cells were performed. CRISPR/Cas9 knockout (p62.1 - protein only) or CRISPR/dCas9-KRAB knockout (p62.2K - mRNA and protein) of p62 in SCC12 cells
2025-07-09 | GSE294764 | GEO