Ligand-binding pockets in RNA, and where to find them [II]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1156226 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30534805_1.fastq.gz | Fastqsanger.gz | |||
| SRR30534805_2.fastq.gz | Fastqsanger.gz | |||
| SRR30534806_1.fastq.gz | Fastqsanger.gz | |||
| SRR30534806_2.fastq.gz | Fastqsanger.gz | |||
| SRR30534807_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 32 |
Similar Datasets
Project description:RNAs are critical regulators of gene expression, and their functions are often mediated by complex secondary and tertiary structures. Structured regions in RNA can selectively interact with small molecules – via well-defined ligand binding pockets – to modulate the regulatory repertoire of an RNA. The broad potential to modulate biological function via RNA-ligand interactions remains unrealized, however, due to challenges in identifying RNA motifs with the ability to bind ligands with good physiochemical properties (often termed drug-like). Here, we devise fpocketR, a computational strategy that accurately detects pockets capable of binding drug-like ligands in RNA structures. Remarkably few, less than 60, of such pockets hadbeen previously visualized. We experimentally confirmed the ligandability of novel pockets detected with fpocketR using a fragment-based approach introduced here, Frag-MaP, that detects ligand-binding sites in cells. Analysis of pockets detected by fpocketR and validated by Frag-MaP reveals dozens of newly identified sites able to bind drug-like ligands, supports a model for RNA secondary structural motifs able to bind quality ligands, and creates a broad framework for understanding the RNA ligand-ome.
2025-04-02 | GSE276279 | GEO
Project description:RNA polymerase II drives mRNA gene expression, yet our understanding of global Pol II repression is limited. Using auxin-inducible degron, we degraded Pol II's RPB1 subunit in mESCs, resulting in global repression, yet certain genes exhibited increased RNA levels post-degradation. These genes are associated with GPCR ligand binding and are characterized by being less paused and comprising polycomb-bound short genes. RPB1 degradation globally increased KDM6B binding, which was insufficient to explain specific gene activation. In contrast, RPB2 degradation repressed nearly all genes, accompanied by decreased H3K9me3 and SUV39H1 occupancy. We observed a specific increase in serine 2 phosphorylated Pol II at Pol II degradation-upregulated genes, indicating their resistance to degradation. Additionally, a-amanitin or UV treatment resulted in RPB1 degradation and global gene repression, unveiling subsets of upregulated genes. Our findings highlight the activation of signaling genes as a potential mechanism for cells to counter global transcription shutdown during stress.
2024-05-28 | PXD048023 |
Project description:Type II nuclear hormone receptors, such as FXR, LXR, and PPAR, which function in glucose and lipid metabolism and serve as drug targets for metabolic diseases, are permanently positioned in the nucleus regardless of the ligand status. Ligand activation of these receptors is thought to occur by co-repressor/co-activator exchange, followed by initiation of transcription. However, recent genome-wide location analysis showed that LXRα and PPARα binding in the liver is largely ligand-dependent. We hypothesized that pioneer factor Foxa2 evicts nucleosomes to enable ligand-dependent receptor binding. We show that chromatin accessibility, FXR binding and LXRα occupancy, and ligand-responsive activation of gene expression by FXR and LXRα require Foxa2. Unexpectedly, Foxa2 occupancy is drastically increased when either receptor, FXR or LXRα, is bound by an agonist. In addition, co-immunoprecipitation experiments demonstrate that Foxa2 interacts with either receptor in a ligand-dependent manner, suggesting that Foxa2 and the receptor bind DNA as an interdependent complex during ligand activation. Furthermore, PPARα binding is induced in Foxa2 mutants treated with FXR and LXR ligands, leading to activation of PPARα targets.
2021-07-12 | GSE149075 | GEO
Project description:RNA-seq of breast cancer cell lines post ligand treatment II
| PRJNA529360 | ENA
Project description:Increasing evidence indicates CD4+ T cells can recognize cancer-specific antigens and control tumor growth. However, it remains difficult to predict the antigens that will be presented by human leukocyte antigen class II molecules (HLA-II) - hindering efforts to optimally target them therapeutically. Obstacles include inaccurate peptide-binding prediction and unsolved complexities of the HLA-II pathway. To address these challenges, we introduce an improved technology for discovering HLA-II binding motifs and conduct a comprehensive analysis of tumor-ligandomes to learn processing rules relevant in the tumor microenvironment (TME). We profiled HLA-II alleles and showed that binding motifs are highly sensitive to HLA-DM, a peptide loading chaperone. We also revealed that intratumoral HLA-II presentation is dominated by professional antigen presenting cells (APCs), rather than cancer cells. Integrating these observations, we developed algorithms that accurately predict APC ligandomes, including peptides from phagocytosed cancer cells. These tools and biological insights will enhance HLA-II directed cancer therapies.
2019-06-18 | MSV000083991 | MassIVE
Project description:The protein Vezf1 plays multiple roles important for embryonic development. In Vezf1-/- mouse embryonic stem (MES) cells our earlier data showed widespread changes in gene expression profiles, including decreased expression of the full length active isoform of Dnmt3b methyltransferase and concomitant genome wide reduction in DNA methylation. Here we show that, in HeLaS3 cells, there is a strong genome-wide correlation between Vezf1 binding and peaks of elongating Ser2-P Pol ll, reflecting Vezf1 dependent slowing of elongation. In Wt MES cells the elongating form of RNA polymerase II accumulates near Vezf1 binding sites within the dnmt3b gene and at several other Vezf1 sites, and this accumulation is significantly reduced at these sites in Vezf1-/- MES cells. Depending upon genomic location, Vezf1 mediated Pol II pausing can have different regulatory roles in transcription and splicing. We find examples of genes in which Vezf1 binding sites are located near cassette exons, and in which loss of Vezf1 leads to a change in the relative abundance of alternatively spliced messages. We further show that Vezf1 interacts with Mrg15/Mrgbp, a protein that recognizes H3K36 tri-methylation, consistent with the role of histone modifications at alternatively spliced sites. Comparison of Vezf1 and RNA Pol II binding in mouse and human cells.
2012-03-09 | E-GEOD-34785 | biostudies-arrayexpress
Project description:Among its many roles in development, retinoic acid determines the anterior-posterior identity of differentiating motor neurons by activating Retinoic Acid Receptor (RAR)-mediated transcription. RAR is thought to bind the genome constitutively, and only induce transcription in the presence of the retinoid ligand. However, little is known about where RAR binds to the genome or how it selects target sites. We tested the constitutive RAR binding model using the retinoic acid-driven differentiation of mouse embryonic stem cells into differentiated motor neurons. We find that retinoic acid treatment results in widespread changes in RAR genomic binding, including novel binding to genes directly responsible for anterior-posterior specification, as well as the subsequent recruitment of the basal polymerase machinery. Finally, we discovered that the binding of transcription factors at the embryonic stem cell stage can accurately predict where in the genome RAR binds after initial differentiation. We have characterized a ligand-dependent shift in RAR genomic occupancy at the initiation of neurogenesis. Our data also suggests that enhancers active in pluripotent embryonic stem cells may be preselecting regions that will be activated by RAR during neuronal differentiation. The differentiation of ventral motor neurons is induced by treating embryonic stem cell cultures with retinoic acid. Here, ChIP-seq is used to profile the genome-wide occupancy of RAR isofroms both immediately prior to and during exposure of the cells to retinoic acid. ChIP-seq is also used to profile the genomic occupancy of Pol2 with phosphorylated serine 5 (Pol2-S5P) and phosphorylated serine 2 (Pol2-S2P) after exposure to retinoic acid.
2010-12-10 | E-GEOD-19409 | biostudies-arrayexpress
Project description:Among its many roles in development, retinoic acid determines the anterior-posterior identity of differentiating motor neurons by activating Retinoic Acid Receptor (RAR)-mediated transcription. RAR is thought to bind the genome constitutively, and only induce transcription in the presence of the retinoid ligand. However, little is known about where RAR binds to the genome or how it selects target sites. We tested the constitutive RAR binding model using the retinoic acid-driven differentiation of mouse embryonic stem cells into differentiated motor neurons. We find that retinoic acid treatment results in widespread changes in RAR genomic binding, including novel binding to genes directly responsible for anterior-posterior specification, as well as the subsequent recruitment of the basal polymerase machinery. Finally, we discovered that the binding of transcription factors at the embryonic stem cell stage can accurately predict where in the genome RAR binds after initial differentiation. We have characterized a ligand-dependent shift in RAR genomic occupancy at the initiation of neurogenesis. Our data also suggests that enhancers active in pluripotent embryonic stem cells may be preselecting regions that will be activated by RAR during neuronal differentiation.
2010-12-10 | GSE19409 | GEO
Project description:Protein coding genes and some of the non-coding RNA genes in eucaryotes are transcribed by RNA Polymerase II. A transcription machinery complex consists of RNA Pol II and many other proteins including transcription factors, activators and repressors of transcription. Pol II binding sites are found in actively transcribing genes and many which are not actively transcribing. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf Map binding sites of RNA Polymerase II in the genome of K562 & NB4 cells
2008-10-02 | E-GEOD-13008 | biostudies-arrayexpress
Project description:CD4 T cells are key for priming and regulating immune recognition of infected and cancer cells, but predictions of class II epitopes have limited accuracy. We profiled over 100’000 HLA-II ligands by Mass Spectrometry and developed a novel motif deconvolution algorithm to analyze these data. Our work demonstrates substantial improvements in the definition of HLA-II binding motifs and enhanced accuracy in HLA-II ligand and class II epitope predictions.
2024-10-18 | MSV000096130 | MassIVE