Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA273389 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The Six1 oncoprotein represses translation of p53 via concomitant regulation of RPL26 and microRNA-27a
| PRJNA274770 | ENA
Project description:TP53 is mutated in 50% of all cancers, and is often functionally compromised in cancers where it is not mutated. We demonstrate that the pro-tumorigenic/metastatic Six1 homeoprotein decreases p53 levels through a mechanism that does not involve the negative regulator of p53, MDM2. Instead, Six1 regulates p53 via a dual mechanism involving upregulation of microRNA-27a and downregulation of the ribosomal protein L26 (RPL26), a positive regulator of p53 translation. Mutation analysis confirms that RPL26, whose expression inversely correlates with Six1 expression in numerous tumor types, inhibits miR-27a binding to the p53 3’UTR and prevents microRNA-mediated translational inhibition of p53. Thus, through simultaneous downregulation of RPL26 and upregulation of miR-27a, Six1 efficiently lowers p53 levels despite regulation of p53 at the level of the proteasome. Consequently, Six1 overexpression, which is observed in numerous tumor types, leads to dramatic resistance to nutlins, as well as other therapies targeting the p53-MDM2 interaction.
2016-01-15 | GSE65200 | GEO
Project description:TP53 is mutated in 50% of all cancers, and is often functionally compromised in cancers where it is not mutated. We demonstrate that the pro-tumorigenic/metastatic Six1 homeoprotein decreases p53 levels through a mechanism that does not involve the negative regulator of p53, MDM2. Instead, Six1 regulates p53 via a dual mechanism involving upregulation of microRNA-27a and downregulation of the ribosomal protein L26 (RPL26), a positive regulator of p53 translation. Mutation analysis confirms that RPL26, whose expression inversely correlates with Six1 expression in numerous tumor types, inhibits miR-27a binding to the p53 3’UTR and prevents microRNA-mediated translational inhibition of p53. Thus, through simultaneous downregulation of RPL26 and upregulation of miR-27a, Six1 efficiently lowers p53 levels despite regulation of p53 at the level of the proteasome. Consequently, Six1 overexpression, which is observed in numerous tumor types, leads to dramatic resistance to nutlins, as well as other therapies targeting the p53-MDM2 interaction.
2016-03-21 | GSE65677 | GEO
Project description:MicroRNAs are well known to mediate translational repression and mRNA degradation in the cytoplasm. Various microRNAs have also been detected in membrane-compartmentalized organelles, but the functional significance has remained elusive. Here we report that miR-1, a microRNA specifically induced during myogenesis, efficiently enters the mitochondria where it unexpectedly stimulates, rather than represses, the translation of specific mitochondrial genome-encoded transcripts. We show that this positive effect requires specific miR:mRNA base-pairing and Ago2, but not its functional partner GW182, which is excluded from the mitochondria. We provide evidence for the direct action of Ago2 in mitochondrial translation by Ago2 CrossLinking ImmunoPrecipitation coupled with sequencing (CLIP-seq), functional rescue with mitochondria-targeted Ago2, and selective inhibition of the microRNA machinery in the cytoplasm. These findings unveil a positive function of microRNA in mitochondrial translation and suggest a highly coordinated myogenic program via miR-1 mediated translational stimulation in the mitochondria and repression in the cytoplasm. Examination of miRNA's regulation function in mitochondria in C2C12 myoblasts cells and myotubes cells with CLIP-seq (Ago2).
2014-08-01 | E-GEOD-57596 | biostudies-arrayexpress
Project description:We have recently confirmed miR-27a-3p as a crucial regulator of human adipogenesis (Wu H, Pula T, Tews D, Amri E-Z, Debatin K-M, Wabitsch M, Fischer-Posovszky P, Roos J. microRNA-27a-3p but Not -5p Is a Crucial Mediator of Human Adipogenesis. Cells. 2021; 10(11):3205. https://doi.org/10.3390/cells10113205 ). MiR-27a-5p did not impair human adipogenesis. However, since several publications state that miR-27a ist also a crucial regulator of UCP1, we were interested if miR-27a-3p or miR-27a-5p regulatas UCP1 and other thermogenesis related genes. We found a strong regulation of UCP1 with functional relevance for the cellular metabolism by miR-27a-5p.To asesse the mRNA gene expression pattern, mRNA sequencing was performed.
2024-06-30 | GSE217629 | GEO
Project description:MicroRNAs are well known to mediate translational repression and mRNA degradation in the cytoplasm. Various microRNAs have also been detected in membrane-compartmentalized organelles, but the functional significance has remained elusive. Here we report that miR-1, a microRNA specifically induced during myogenesis, efficiently enters the mitochondria where it unexpectedly stimulates, rather than represses, the translation of specific mitochondrial genome-encoded transcripts. We show that this positive effect requires specific miR:mRNA base-pairing and Ago2, but not its functional partner GW182, which is excluded from the mitochondria. We provide evidence for the direct action of Ago2 in mitochondrial translation by Ago2 CrossLinking ImmunoPrecipitation coupled with sequencing (CLIP-seq), functional rescue with mitochondria-targeted Ago2, and selective inhibition of the microRNA machinery in the cytoplasm. These findings unveil a positive function of microRNA in mitochondrial translation and suggest a highly coordinated myogenic program via miR-1 mediated translational stimulation in the mitochondria and repression in the cytoplasm.
2014-08-01 | GSE57596 | GEO
Project description:Pluripotent stem cell identities such as differentiation and infinite proliferation have long been decoded in the frameworks of transcription factor networks, epigenomes, and signal transduction, yet unclear and fragmented. However, directing attention toward translation regulation, the bridge between these events promises to provide new insights into previously unexplained mechanisms. Functional screening led to the discovery that EIF3D maintains primed pluripotency via selective translation regulation. The loss of EIF3D unbalanced the pluripotency-associated signaling pathways, disrupting primed pluripotency. Furthermore, we found that EIF3D safeguards robust proliferation by managing the translation of multiple p53 regulators that maintain low p53 activity in the undifferentiated state. Therefore, this study provides a paradigm for selective translation regulation that defines the primed pluripotent stem cell identity.
2025-04-10 | GSE248702 | GEO
Project description:Pluripotent stem cell identities such as differentiation and infinite proliferation have long been decoded in the frameworks of transcription factor networks, epigenomes, and signal transduction, yet unclear and fragmented. However, directing attention toward translation regulation, the bridge between these events promises to provide new insights into previously unexplained mechanisms. Functional screening led to the discovery that EIF3D maintains primed pluripotency via selective translation regulation. The loss of EIF3D unbalanced the pluripotency-associated signaling pathways, disrupting primed pluripotency. Furthermore, we found that EIF3D safeguards robust proliferation by managing the translation of multiple p53 regulators that maintain low p53 activity in the undifferentiated state. Therefore, this study provides a paradigm for selective translation regulation that defines the primed pluripotent stem cell identity.
2025-04-10 | GSE249191 | GEO
Project description:Pluripotent stem cell identities such as differentiation and infinite proliferation have long been decoded in the frameworks of transcription factor networks, epigenomes, and signal transduction, yet unclear and fragmented. However, directing attention toward translation regulation, the bridge between these events promises to provide new insights into previously unexplained mechanisms. Functional screening led to the discovery that EIF3D maintains primed pluripotency via selective translation regulation. The loss of EIF3D unbalanced the pluripotency-associated signaling pathways, disrupting primed pluripotency. Furthermore, we found that EIF3D safeguards robust proliferation by managing the translation of multiple p53 regulators that maintain low p53 activity in the undifferentiated state. Therefore, this study provides a paradigm for selective translation regulation that defines the primed pluripotent stem cell identity.
2025-04-10 | GSE249190 | GEO
Project description:Pluripotent stem cell identities such as differentiation and infinite proliferation have long been decoded in the frameworks of transcription factor networks, epigenomes, and signal transduction, yet unclear and fragmented. However, directing attention toward translation regulation, the bridge between these events promises to provide new insights into previously unexplained mechanisms. Functional screening led to the discovery that EIF3D maintains primed pluripotency via selective translation regulation. The loss of EIF3D unbalanced the pluripotency-associated signaling pathways, disrupting primed pluripotency. Furthermore, we found that EIF3D safeguards robust proliferation by managing the translation of multiple p53 regulators that maintain low p53 activity in the undifferentiated state. Therefore, this study provides a paradigm for selective translation regulation that defines the primed pluripotent stem cell identity.
2025-04-10 | GSE248819 | GEO