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Systematic Identification of Post-Transcriptional Regulatory Modules

ABSTRACT: 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.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Vishvak Subramanyam

LAB HEAD: Hani Goodarzi

PROVIDER: PXD041608 | Pride | 2024-08-09

REPOSITORIES: Pride

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			Action	DRS
	AGGF1_negative_1.raw	Raw
	AGGF1_negative_2.raw	Raw
	AGGF1_negative_3.raw	Raw
	AGGF1_positive_1.raw	Raw
	AGGF1_positive_2.raw	Raw

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