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A Unified Framework for Systematic Identification of Post-Transcriptional Regulatory Modules

ABSTRACT: A Unified Framework for Systematic Identification of Post-Transcriptional Regulatory Modules

PROVIDER: PRJNA937646 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23585000.fastq.gz	Fastqsanger.gz
	SRR23585001.fastq.gz	Fastqsanger.gz
	SRR23585002.fastq.gz	Fastqsanger.gz
	SRR23585003.fastq.gz	Fastqsanger.gz
	SRR23585004.fastq.gz	Fastqsanger.gz

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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.

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A Unified Framework for Systematic Identification of Post-Transcriptional Regulatory Modules

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-02-21 | GSE225809 | GEO

Systematic Identification of Post-Transcriptional Regulatory Modules

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

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