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FeaSion Uncovers the Multifaceted Co-transcriptional Roles of RNAPII CTD Phosphorylation Regulated by Cancer Hallmark Genes

ABSTRACT: The phosphorylation of RNAPII's C-terminal domain (CTD) has been extensively studied, yet functional investigations into all five known phosphorylation states (pY1, pS2, pT4, pS5, pS7) simultaneously are scarce, and the number of identified regulators is limited. Utilizing the FeaSion (Feature-Screening-Function) strategy, we characterized RNAPII CTD phosphorylation by identifying 706 interactors across these five states. Additionally, we conducted a CRISPR-FACS screen, revealing 2,067 potential regulators, which include 79 cancer hallmark genes, 94 kinases, and 21 phosphatases. Our study demonstrates that mutations at these phosphorylation sites broadly influence various transcriptional processes and preferentially alter co-transcriptional events, including histone modifications (H3K36me3, H2AZ, H2AZ.ac) and RNA splicing. This work offers a comprehensive perspective on RNAPII CTD phosphorylation and its regulatory network, presenting a valuable resource for future research in developmental biology and disease mechanisms.

ORGANISM(S): Homo Sapiens

SUBMITTER: Xiong Ji

PROVIDER: PXD059705 | iProX | Fri Jan 10 00:00:00 GMT 2025

REPOSITORIES: iProX

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