Similar Datasets
Project description:RNA-binding proteins (RBPs) are multifunctional regulators of gene expression with complex and context-dependent mechanisms of action, yet the regulatory grammar that underlies RBP-mediated functions remains underexplored. Here, we performed a multi-omic data integration to systematically decipher the context-specific functions of RBPs. First, we report a compendium of in vivo proximity-dependent biotinylation (BioID) datasets of 50 human RBPs, which we used to generate a large-scale map of RBP protein neighborhoods. In parallel, we took advantage of CRISPR-interference with single-cell RNA-seq read-out (Perturb-seq) to capture rich transcriptomic phenotypes downstream of each RBP knockdown. By combining these physical and functional interaction readouts, along with the ENCODE transcriptome-wide atlas of RBP binding sites from eCLIP assays, we generated an integrated map of functional RBP interactions. This map not only captures well-studied post-transcriptional processes, but also reveals numerous previously unknown RBP-mediated regulatory functions. For a number of these cases, we have validated their predicted context-specific RBP functions using biochemical and genetic approaches. By deciphering these complex modes of functional interactions between RBPs, we have taken the first step towards a more comprehensive understanding of post-transcriptional regulatory processes and their underlying molecular grammar.
2024-09-30 | GSE274049 | GEO
Project description:RNA-binding proteins (RBPs) are multifunctional regulators of gene expression with complex and context-dependent mechanisms of action, yet the regulatory grammar that underlies RBP-mediated functions remains underexplored. Here, we performed a multi-omic data integration to systematically decipher the context-specific functions of RBPs. First, we report a compendium of in vivo proximity-dependent biotinylation (BioID) datasets of 50 human RBPs, which we used to generate a large-scale map of RBP protein neighborhoods. In parallel, we took advantage of CRISPR-interference with single-cell RNA-seq read-out (Perturb-seq) to capture rich transcriptomic phenotypes downstream of each RBP knockdown. By combining these physical and functional interaction readouts, along with the ENCODE transcriptome-wide atlas of RBP binding sites from eCLIP assays, we generated an integrated map of functional RBP interactions. This map not only captures well-studied post-transcriptional processes, but also reveals numerous previously unknown RBP-mediated regulatory functions. For a number of these cases, we have validated their predicted context-specific RBP functions using biochemical and genetic approaches. By deciphering these complex modes of functional interactions between RBPs, we have taken the first step towards a more comprehensive understanding of post-transcriptional regulatory processes and their underlying molecular grammar.
2024-02-21 | GSE225807 | GEO
Project description:RNA-binding proteins (RBPs) are multifunctional regulators of gene expression with complex and context-dependent mechanisms of action, yet the regulatory grammar that underlies RBP-mediated functions remains underexplored. Here, we performed a multi-omic data integration to systematically decipher the context-specific functions of RBPs. First, we report a compendium of in vivo proximity-dependent biotinylation (BioID) datasets of 50 human RBPs, which we used to generate a large-scale map of RBP protein neighborhoods. In parallel, we took advantage of CRISPR-interference with single-cell RNA-seq read-out (Perturb-seq) to capture rich transcriptomic phenotypes downstream of each RBP knockdown. By combining these physical and functional interaction readouts, along with the ENCODE transcriptome-wide atlas of RBP binding sites from eCLIP assays, we generated an integrated map of functional RBP interactions. This map not only captures well-studied post-transcriptional processes, but also reveals numerous previously unknown RBP-mediated regulatory functions. For a number of these cases, we have validated their predicted context-specific RBP functions using biochemical and genetic approaches. By deciphering these complex modes of functional interactions between RBPs, we have taken the first step towards a more comprehensive understanding of post-transcriptional regulatory processes and their underlying molecular grammar.
2024-02-21 | GSE225808 | GEO
Project description:RNA-binding proteins (RBPs) are multifunctional regulators of gene expression with complex and context-dependent mechanisms of action, yet the regulatory grammar that underlies RBP-mediated functions remains underexplored. Here, we performed a multi-omic data integration to systematically decipher the context-specific functions of RBPs. First, we report a compendium of in vivo proximity-dependent biotinylation (BioID) datasets of 50 human RBPs, which we used to generate a large-scale map of RBP protein neighborhoods. In parallel, we took advantage of CRISPR-interference with single-cell RNA-seq read-out (Perturb-seq) to capture rich transcriptomic phenotypes downstream of each RBP knockdown. By combining these physical and functional interaction readouts, along with the ENCODE transcriptome-wide atlas of RBP binding sites from eCLIP assays, we generated an integrated map of functional RBP interactions. This map not only captures well-studied post-transcriptional processes, but also reveals numerous previously unknown RBP-mediated regulatory functions. For a number of these cases, we have validated their predicted context-specific RBP functions using biochemical and genetic approaches. By deciphering these complex modes of functional interactions between RBPs, we have taken the first step towards a more comprehensive understanding of post-transcriptional regulatory processes and their underlying molecular grammar.
2024-02-21 | GSE225806 | GEO
Project description:In our cells, a limited number of RNA binding proteins (RBPs) are responsible for all aspects of RNA metabolism across the entire transcriptome. To accomplish this, RBPs form regulatory units that act on specific target regulons. However, the landscape of RBP combinatorial interactions remains poorly explored. Here, we performed a systematic annotation of RBP combinatorial interactions via multimodal data integration. We built a large-scale map of RBP protein neighborhoods by generating in vivo proximity-dependent biotinylation datasets of 50 human RBPs. In parallel, we used CRISPR interference with single-cell readout to capture transcriptomic changes upon RBP knockdowns. By combining these physical and functional interaction readouts, along with the atlas of RBP mRNA targets from eCLIP assays, we generated an integrated map of functional RBP interactions. We then used this map to match RBPs to their context-specific functions and validated the predicted functions biochemically for four RBPs. This study highlights the previously underappreciated scale of the inter-RBP interactions, be it genetic or physical, and is a first step towards a more comprehensive understanding of post-transcriptional regulatory processes and their underlying molecular grammar.
2024-08-09 | PXD041608 | Pride
Project description:Transcription factors (TFs) combine with co-factors to form transcriptional regulatory modules (TRMs) that regulate gene expression programs with spatiotemporal specificity. Here we present a novel and generic method (rTRM) for the reconstruction of TRMs that integrates genomic information from TF binding, cell type-specific gene expression and protein-protein interactions. rTRM was applied to reconstruct the TRMs specific for embryonic stem cells (ESC) and hematopoietic stem cells (HSC), neural progenitor cells, trophoblast stem cells and distinct types of terminally differentiated CD4(+) T cells. The ESC and HSC TRM predictions were highly precise, yielding 77 and 96 proteins, of which ?75% have been independently shown to be involved in the regulation of these cell types. Furthermore, rTRM successfully identified a large number of bridging proteins with known roles in ESCs and HSCs, which could not have been identified using genomic approaches alone, as they lack the ability to bind specific DNA sequences. This highlights the advantage of rTRM over other methods that ignore PPI information, as proteins need to interact with other proteins to form complexes and perform specific functions. The prediction and experimental validation of the co-factors that endow master regulatory TFs with the capacity to select specific genomic sites, modulate the local epigenetic profile and integrate multiple signals will provide important mechanistic insights not only into how such TFs operate, but also into abnormal transcriptional states leading to disease.
| S-EPMC3874207 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-07-01 | E-GEOD-67838 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-11-27 | E-GEOD-51050 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2015-07-01 | GSE67838 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-04-21 | GSE199486 | GEO