ArticleScience advances2025
FeaSion decodes the regulatory landscape and functional diversity of RNA polymerase II CTD phosphorylation.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Communication is key: combinatorial phosphorylation and functional cross-talk in the RNA polymerase II CTD code.Biochemical Society transactions · 2026Review
- CTDP1 governs a Pol II phosphorylation intermediate and coordinates Mediator recruitment, transcription efficiency, and splicing.Nucleic acids research · 2026Article
- Kaposi's Sarcoma-associated herpesvirus uses a novel protein fold to hijack RNA Polymerase II for viral late gene transcription.bioRxiv : the preprint server for biology · 2026Article
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RNA polymerase II's (RNAPII) C-terminal domain (CTD) contains five phosphorylation sites (pY1, pS2, pT4, pS5, and pS7). However, their regulatome and immediate functions remain elusive. Using the FeaSion (Feature-Screening-Function) strategy, we mapped RNAPII phosphorylation site-specific interactors and genomic occupancy, revealing links to preferential gene length, exon number, and transcription factor binding. CRISPR-FACS screens identified different candidate regulators modulating individual phosphorylation sites. Rapid replacement showed site-specific mutations influence different transcriptional processes, histone modifications (H3K36me3 and H2A.Zac), and preferentially affect developmental and signaling genes. Moreover, we demonstrate kinases CLK1/4 and YES1 directly regulate RNAPII transcription-via site-specific CTD phosphorylation-to control developmental, metabolic, and signal transduction programs. Our findings reveal an expanded regulatory network involving >100 kinase and phosphatases that potentially orchestrate CTD phosphorylation beyond their canonical functions, establishing a multilayered phospho-regulatory network with broad implications for gene expression control in development and disease.
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