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CBC

Structure-function study of the nuclear cap-binding complex mediated RNA export
Funder: French National Research Agency (ANR)Project code: ANR-24-CE11-4977
Funder Contribution: 451,702 EUR
Description

Eukaryotic transcription produces large amounts of RNA, with some being processed and exported to the cytoplasm, while others are aberrant and eliminated in the nucleus. The nuclear cap-binding complex (CBC) plays a pivotal role in these processes. During early transcription, RNA-bound CBC forms a complex with the ARS2 protein (CBCA). To influence the fate of transcripts, various proteins, referred to as RNA 'effectors', compete for interactions with CBCA to ultimately direct transcripts towards processing, export, or degradation. Among them are PHAX, notably responsible for the nuclear export of snRNAs, as well as NCBP3 and hnRNPC, involved in mRNA export. However, the molecular mechanisms governing the competition between these effectors, and their organisation within CBC higher order complexes remain unclear. The primary goal of the project is to characterize, structurally and functionally, these essential CBC-mediated RNA sorting mechanisms, focusing on the role of PHAX, NCBP3 and hnRNPC. To achieve this ambitious goal, the project will rely on a collaborative effort of three partners with complementary expertise and promising preliminary results. The proposed work will thus expand our understanding of this fundamental regulatory mechanism in eukaryotic gene expression.

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