Similar Datasets
Project description:RIPChip ELAVL1 binding mRNA levels change by GnRH in LbetaT2 cells
| PRJNA526493 | ENA
Project description:Post-transcriptional gene regulation by miRNAs and RNA binding proteins (RBP) is important in development, physiology and disease. To examine the interplay between miRNAs and the RBP ELAVL1 (a.k.a. HuR), we mapped miRNA binding sites on a transcriptome-wide scale in WT and Elavl1 knockout murine bone marrow-derived macrophages. Proximity of ELAVL1 binding sites attenuated miRNA binding to transcripts and promoted gene expression. Transcripts that regulate angiogenesis and macrophage/ endothelial cross talk were preferentially targeted by miRNAs, suggesting that ELAVL1 promotes angiogenesis, at least in part, by antagonism of miRNA function. We found that ELAVL1 antagonized binding of miR-27 to the 3’UTR of Zfp36 mRNA and alleviated miR-27-mediated suppression of the RBP ZFP36 (a.k.a. Tristetraprolin). Thus the miR-27-regulated mechanism synchronizes the expression of ELAVL1 and ZFP36. This study provides a resource for systems-level interrogation of post-transcriptional gene regulation in macrophages, a key cell type in inflammation, angiogenesis and tissue homeostasis.
2015-04-23 | GSE63199 | GEO
Project description:Post-transcriptional gene regulation by miRNAs and RNA binding proteins (RBP) is important in development, physiology and disease. To examine the interplay between miRNAs and the RBP ELAVL1 (a.k.a. HuR), we mapped miRNA binding sites on a transcriptome-wide scale in WT and Elavl1 knockout murine bone marrow-derived macrophages. Proximity of ELAVL1 binding sites attenuated miRNA binding to transcripts and promoted gene expression. Transcripts that regulate angiogenesis and macrophage/ endothelial cross talk were preferentially targeted by miRNAs, suggesting that ELAVL1 promotes angiogenesis, at least in part, by antagonism of miRNA function. We found that ELAVL1 antagonized binding of miR-27 to the 3’UTR of Zfp36 mRNA and alleviated miR-27-mediated suppression of the RBP ZFP36 (a.k.a. Tristetraprolin). Thus the miR-27-regulated mechanism synchronizes the expression of ELAVL1 and ZFP36. This study provides a resource for systems-level interrogation of post-transcriptional gene regulation in macrophages, a key cell type in inflammation, angiogenesis and tissue homeostasis. Bone marrow derived macrpohges mRNA profiles of 7-day cultured wild type (WT) and Elavl1l-/- mouse bone marrow cells were generated by deep sequencing, with 4 biologic duplication, using Illumina GAII.
2015-04-23 | E-GEOD-63199 | biostudies-arrayexpress
Project description:Gonadotropin secretion, which is elicited by GnRH stimulation of the anterior pituitary gonadotropes, is a critical feature of reproductive control and the maintenance of fertility. In addition, activation of the GnRH receptor (GnRHR) regulates transcription and translation of multiple factors that regulate the signaling response and synthesis of gonadotropins. GnRH stimulation results in a broad redistribution of mRNA between active and inactive polyribosomes within the cell, but the mechanism of redistribution is not known. The RNA-binding protein embryonic lethal, abnormal vision, Drosophila-like 1 (ELAVL1) binds to AU-rich elements in mRNA and is one of the most abundant mRNA-binding proteins in eukaryotic cells. It is known to serve as a core component of RNA-binding complexes that direct the fate of mRNA. In LβT2 gonadotropes, we showed that ELAVL1 binds to multiple mRNAs encoding factors that are crucial for gonadotropin synthesis and release. Association with some mRNAs is GnRH sensitive but does not correlate with abundance of binding. We also showed MAPK-dependent changes in intracellular localization of ELAVL1 in response to GnRH stimulation. Knockdown of ELAVL1 gene expression resulted in reduced Lhb and Gnrhr mRNA levels, reduced cell surface expression of GnRHR, and reduced LH secretion in response to GnRH stimulation. Overall, these observations not only support the role of ELAVL1 in GnRHR-mediated regulation of gene expression and LH secretion but also indicate that other factors may contribute to the precise fate of mRNA in response to GnRH stimulation of gonadotropes.
| S-EPMC6660905 | biostudies-literature
Project description:Upon detection of a pathogen, the innate immune system triggers signaling events leading to the transcription of mRNAs that encode for pro-inflammatory and anti-microbial effectors. RNA-binding proteins (RBPs) interact with these functionally critical mRNAs and temporally regulate their fates at the post-transcriptional level. One such RBP is ELAVL1, which is known to bind to introns and 3’UTRs. While significant progress has been made in understanding how ELAVL1 regulates mRNAs, how its target repertoire and binding affinity changes within an immunological context remains poorly understood. Here, we overlap four distinct high-throughput approaches to define its cell-type and context-dependent targets and determine its regulatory impact during immune activation. ELAVL1 overwhelmingly binds to intronic sites in a naïve state, but during an innate immune response, ELAVL1 targets the 3’UTR binding both previously and newly expressed mRNAs. We find that ELAVL1 mediates the RNA stability of genes that regulate the pathways involved in pathogen sensing and cytokine production. Our findings reveal the importance of examining RBP regulatory impact under dynamic transcriptomic events to best understand their post-transcriptional regulatory roles within specific biological circuitries.
2020-09-01 | GSE157052 | GEO
Project description:We report the application of RIP-sequencing technology for high-throughput profiling of ELAVL1 protein on the effect of lncRNA an mRNA in WS1 cells after 5 Gy X-ray irradiation
2018-07-20 | GSE102146 | GEO
Project description:Affymetrix gene expression profiling in cumulus cells (CC) retrieved from patients undergoing GnRH agonists and GnRH antagonists IVF treatment. Oocytes from three different maturity stages were considered: metaphase I oocytes (MI), nonfertilized metaphase II (MII) oocytes (MII-NF) and MII oocytes developed to blactocyst stage embryo (MII-BL). From 4 GnRH agonist treated patients, CC MI, CC MII-NF and CC MII-BL samples were collected; from 5 GnRH agonist and 6 GnRH antagonist treated patients, CC MII-NF and CC MII-BL samples were collected; and from 2 GnRH agonist and 4 GnRH antagonist treated patients, CC MI and CC MII-BL were collected. Altogether, 10 CC MI, 15 CC MII-NF and 21 CC MII-BL were collected and considered for transcriptome analysis.
2013-09-13 | E-GEOD-34230 | biostudies-arrayexpress
Project description:This experiment aims to map the HuR (ELAVL1) binding to the global transcriptome in HEK293 cells.
2023-04-30 | E-MTAB-11854 | biostudies-arrayexpress
Project description:ELAVL1 and CELF1 are two RNA-binding proteins involved in alternative splicing control. To address their functional relationships, we identify the differentially spliced mRNAs upon depletion of CELF1, ELAVL1, or both. These proteins control similar sets of genes with similar consequences on exon inclusion or skipping. The magnitude of the effect of the double depletion equals the sum of the magnitudes of the individual depletions, showing that CELF1 and ELAVL1 additively control their target RNAs. CELF1 and ELAVL1 regulated splicing events include ACSL4, WNK1, CD44, MICAL3, and JDP2. Using FRET, we find that CELF1 and ELAVL1 directly interact in cell nuclei. We demonstrate that the combined levels of CELF1 and ELAVL1 is a valuable biomarker in breast cancer, while their levels bring very limited information when taken individually. A “co-RNA splicing map” of CELF1 and ELAVL1 shows they repress alternative splice sites when bound nearby, but activate them when bound further away. Together, these data point to strong functional interactions between CELF1 and ELAVL1 to control alternative splicing with significant impacts in human pathology.
2021-08-01 | GSE118981 | GEO
Project description:RNA binding protein (RBP)-directed post-transcriptional control of stem cell fate represents an underexplored mechanism driving hematopoietic stemness and transformation. We show that a unique set of RBPs are specifically enriched in leukemic stem cells (LSCs) of human primary acute myeloid leukemia (AML) but repressed in normal hematopoietic stem cells. Using an in vivo CRISPR-Cas9-mediated screening approach, we identify 33 key RBPs specifically essential for LSC-mediated MLL-AF9/NrasG12D AML. Knock-down/genetic ablation of the hit RBP Elavl1 in genetically distinct leukemias significantly reduced LSC numbers, and hampered leukemic engraftment. In human AML we show impairment of LSC-driven in vivo leukemic reconstitution and selective depletion of AML progenitors upon ELAVL1 targeting, highlighting the potential clinical importance of our findings. Profiling of the leukemic ELAVL1-mRNA interactome revealed hematopoietic differentiation, RNA splicing and mitochondrial metabolism as major pathways impacted by ELAVL1. Altogether, this work demonstrates that Elavl1 and other RBPs are critical regulators of LSC-survival and self-renewal.
2023-01-18 | GSE127944 | GEO