Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA257975 | ENA |
REPOSITORIES: ENA
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Project description:Expression data from specific translational activity and cytoplasmic localization (nuclear retention) of mRNAs of primary mouse embryonic fibroblasts (MEF) early in response to serum. The goal of the study was to roughly discriminate between different levels of RNA regulation, namely mRNA de-novo transcription, mRNA stability and degradation, mRNA nuclear retention, mRNA translation as well as miRNA expression within a defined cellular system and time point and to link these levels together in order to get a more detailed analysis of the complex RNA regulation system, the ?RNA regulome?. To make the data more stringent the same microarray platform (Affymetrix GeneChip system) for all analyses except the miRNA expression profiling were used. Nuclear and cytoplasmic RNA fractions were separated in order to get more insight into potential nuclear retention of mRNAs. In addition the cytoplasmic mRNA pool was fractionated by its polyribosomal load using sucrose density gradients. Likewise the small RNA was specifically analyzed for miRNA precursor expression and mature miRNA expression. As study system the early serum response model of primary mouse embryonal fibroblast cells was used. Affymetrix GeneChip microarrays were used to detail regulatory mechanisms of mRNA translation and localization in response to serum (2h). Experiment Overall Design: The gene expression and regulation program at the RNA level early (2h) in response to serum was studied. mRNAs was isolated from serum starved and 2h serum treated MEF cells. This experiment allowed detailed regulatory mechanisms of mRNA translational activity and cytoplasmic localization (nuclear retention) of mRNAs of MEF cells in early response to serum.
2008-06-15 | E-GEOD-7363 | biostudies-arrayexpress
Project description:Messenger RNA is thought to predominantly reside in the cytoplasm, where it is translated and eventually degraded. Although nuclear retention of mRNA has a regulatory potential it is considered extremely rare in mammals. Here to explore the extent of mRNA retention in metabolic tissues we combine deep sequencing of nuclear and cytoplasmic RNA fractions with single molecule transcript imaging in mouse beta cells, liver and gut. We identify a wide range of protein coding genes for which the levels of spliced polyadenylated mRNA are higher in the nucleus than in the cytoplasm. These include genes such as the transcription factor ChREBP, Nlrp6, Glucokinase and Glucagon receptor. We demonstrate that nuclear retention of mRNA can efficiently buffer cytoplasmic transcript levels from noise that emanates from transcriptional bursts. Our study challenges the view that transcripts predominantly reside in the cytoplasm and reveals a role of the nucleus in dampening gene expression noise.
2015-11-13 | GSE73977 | GEO
Project description:Expression data from specific translational activity and cytoplasmic localization (nuclear retention) of mRNAs of primary mouse embryonic fibroblasts (MEF) early in response to serum. The goal of the study was to roughly discriminate between different levels of RNA regulation, namely mRNA de-novo transcription, mRNA stability and degradation, mRNA nuclear retention, mRNA translation as well as miRNA expression within a defined cellular system and time point and to link these levels together in order to get a more detailed analysis of the complex RNA regulation system, the ?RNA regulome?. To make the data more stringent the same microarray platform (Affymetrix GeneChip system) for all analyses except the miRNA expression profiling were used. Nuclear and cytoplasmic RNA fractions were separated in order to get more insight into potential nuclear retention of mRNAs. In addition the cytoplasmic mRNA pool was fractionated by its polyribosomal load using sucrose density gradients. Likewise the small RNA was specifically analyzed for miRNA precursor expression and mature miRNA expression. As study system the early serum response model of primary mouse embryonal fibroblast cells was used. Affymetrix GeneChip microarrays were used to detail regulatory mechanisms of mRNA translation and localization in response to serum (2h). Keywords: treatment experiment
2007-03-27 | GSE7363 | GEO
Project description:Global downregulation of microRNAs (miRNAs) is commonly observed in human cancers and can have a causative role in tumorigenesis. The mechanisms responsible for this phenomenon remain poorly understood. Here we show that YAP, the downstream target of the tumor-suppressive Hippo signaling pathway regulates miRNA biogenesis in a cell density-dependent manner. At low cell density, nuclear YAP binds and sequesters p72 (DDX17), a regulatory component of the miRNA processing machinery. At high cell density, Hippo-mediated cytoplasmic retention of YAP facilitates p72 association with Microprocessor and binding to a specific sequence motif in pri-miRNAs. Inactivation of the Hippo pathway or expression of constitutively active YAP causes widespread miRNA suppression in cells and tumors and a corresponding post-transcriptional induction of MYC expression. Thus, the Hippo pathway links contact-inhibition regulation to miRNA biogenesis and may be responsible for the widespread miRNA repression observed in cancer. Two conditions (Low density and High density) were analyzed in duplicate.
2014-03-03 | E-GEOD-52187 | biostudies-arrayexpress
Project description:Global downregulation of microRNAs (miRNAs) is commonly observed in human cancers and can have a causative role in tumorigenesis. The mechanisms responsible for this phenomenon remain poorly understood. Here we show that YAP, the downstream target of the tumor-suppressive Hippo signaling pathway regulates miRNA biogenesis in a cell density-dependent manner. At low cell density, nuclear YAP binds and sequesters p72 (DDX17), a regulatory component of the miRNA processing machinery. At high cell density, Hippo-mediated cytoplasmic retention of YAP facilitates p72 association with Microprocessor and binding to a specific sequence motif in pri-miRNAs. Inactivation of the Hippo pathway or expression of constitutively active YAP causes widespread miRNA suppression in cells and tumors and a corresponding post-transcriptional induction of MYC expression. Thus, the Hippo pathway links contact-inhibition regulation to miRNA biogenesis and may be responsible for the widespread miRNA repression observed in cancer. Four conditions (siCtrl, si p72, siNF2/LATS2 and siDROSHA/DGCR8) were analyzed in duplicate.
2014-03-03 | E-GEOD-52186 | biostudies-arrayexpress
Project description:Global downregulation of microRNAs (miRNAs) is commonly observed in human cancers and can have a causative role in tumorigenesis. The mechanisms responsible for this phenomenon remain poorly understood. Here we show that YAP, the downstream target of the tumor-suppressive Hippo signaling pathway regulates miRNA biogenesis in a cell density-dependent manner. At low cell density, nuclear YAP binds and sequesters p72 (DDX17), a regulatory component of the miRNA processing machinery. At high cell density, Hippo-mediated cytoplasmic retention of YAP facilitates p72 association with Microprocessor and binding to a specific sequence motif in pri-miRNAs. Inactivation of the Hippo pathway or expression of constitutively active YAP causes widespread miRNA suppression in cells and tumors and a corresponding post-transcriptional induction of MYC expression. Thus, the Hippo pathway links contact-inhibition regulation to miRNA biogenesis and may be responsible for the widespread miRNA repression observed in cancer. Two conditions (siCtrl and siYAP) were analyzed in duplicate.
2014-03-03 | E-GEOD-52188 | biostudies-arrayexpress
Project description:Global downregulation of microRNAs (miRNAs) is commonly observed in human cancers and can have a causative role in tumorigenesis. The mechanisms responsible for this phenomenon remain poorly understood. Here we show that YAP, the downstream target of the tumor-suppressive Hippo signaling pathway regulates miRNA biogenesis in a cell density-dependent manner. At low cell density, nuclear YAP binds and sequesters p72 (DDX17), a regulatory component of the miRNA processing machinery. At high cell density, Hippo-mediated cytoplasmic retention of YAP facilitates p72 association with Microprocessor and binding to a specific sequence motif in pri-miRNAs. Inactivation of the Hippo pathway or expression of constitutively active YAP causes widespread miRNA suppression in cells and tumors and a corresponding post-transcriptional induction of MYC expression. Thus, the Hippo pathway links contact-inhibition regulation to miRNA biogenesis and may be responsible for the widespread miRNA repression observed in cancer. Two conditions (normal epidermal cells and oncogenic epidermal cells expressing YAP S127A mutant) were analyzed in duplicate.
2014-03-03 | E-GEOD-52206 | biostudies-arrayexpress
Project description:Global downregulation of microRNAs (miRNAs) is commonly observed in human cancers and can have a causative role in tumorigenesis. The mechanisms responsible for this phenomenon remain poorly understood. Here we show that YAP, the downstream target of the tumor-suppressive Hippo signaling pathway regulates miRNA biogenesis in a cell density-dependent manner. At low cell density, nuclear YAP binds and sequesters p72 (DDX17), a regulatory component of the miRNA processing machinery. At high cell density, Hippo-mediated cytoplasmic retention of YAP facilitates p72 association with Microprocessor and binding to a specific sequence motif in pri-miRNAs. Inactivation of the Hippo pathway or expression of constitutively active YAP causes widespread miRNA suppression in cells and tumors and a corresponding post-transcriptional induction of MYC expression. Thus, the Hippo pathway links contact-inhibition regulation to miRNA biogenesis and may be responsible for the widespread miRNA repression observed in cancer. Two conditions (liver normal tissues and liver tumors) were analyzed in duplicate.
2014-03-03 | E-GEOD-52207 | biostudies-arrayexpress
Project description:Global downregulation of microRNAs (miRNAs) is commonly observed in human cancers and can have a causative role in tumorigenesis. The mechanisms responsible for this phenomenon remain poorly understood. Here we show that YAP, the downstream target of the tumor-suppressive Hippo signaling pathway regulates miRNA biogenesis in a cell density-dependent manner. At low cell density, nuclear YAP binds and sequesters p72 (DDX17), a regulatory component of the miRNA processing machinery. At high cell density, Hippo-mediated cytoplasmic retention of YAP facilitates p72 association with Microprocessor and binding to a specific sequence motif in pri-miRNAs. Inactivation of the Hippo pathway or expression of constitutively active YAP causes widespread miRNA suppression in cells and tumors and a corresponding post-transcriptional induction of MYC expression. Thus, the Hippo pathway links contact-inhibition regulation to miRNA biogenesis and may be responsible for the widespread miRNA repression observed in cancer. Two conditions (transfection of p72 or control EGFP in addition to siRNAs for NF2 and LATS2) were analyzed in duplicate.
2014-03-03 | E-GEOD-52205 | biostudies-arrayexpress
Project description:Purpose: MicroRNAs have well characterized roles in cytoplasmic gene regulation by binding mRNA and inhibiting translation. However, besides this post-transcriptional gene silencing, miRNAs have also been implicated in transcriptional gene regulation and alternative splicing, events that are restricted to the cell nucleus. The nuclear functions of miRNAs are currently not understood, and there is a paucity of systematic studies of miRNA nuclear-cytoplasmic distribution and fewer still which have investigated this in the context of physiological conditions. Methods: Here we performed nuclear-cytoplasmic fractionation in a mouse endothelial cell line in hypoxia and characterized the localization of miRNAs using small RNA sequencing. Results: We show here that there is a broad population of mature miRNAs in the cell nucleus and that it is also altered upon exposure to hypoxia. Conclusions: Our results strongly imply that miRNAs have extensive regulatory functions in the nucleus and expand potential therapeutic use of small RNA molecules.
2019-07-17 | GSE125390 | GEO