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- Title
Variation of C-terminal domain governs RNA polymerase II genomic locations and alternative splicing in eukaryotic transcription.
- Authors
Zhang, Qian; Kim, Wantae; Panina, Svetlana B.; Mayfield, Joshua E.; Portz, Bede; Zhang, Y. Jessie
- Abstract
The C-terminal domain of RPB1 (CTD) orchestrates transcription by recruiting regulators to RNA Pol II upon phosphorylation. With CTD driving condensate formation on gene loci, the molecular mechanism behind how CTD-mediated recruitment of transcriptional regulators influences condensates formation remains unclear. Our study unveils that phosphorylation reversibly dissolves phase separation induced by the unphosphorylated CTD. Phosphorylated CTD, upon specific association with transcription regulators, forms distinct condensates from unphosphorylated CTD. Functional studies demonstrate CTD variants with diverse condensation properties exhibit differences in promoter binding and mRNA co-processing in cells. Notably, varying CTD lengths influence the assembly of RNA processing machinery and alternative splicing outcomes, which in turn affects cellular growth, linking the evolution of CTD variation/length with the complexity of splicing from yeast to human. These findings provide compelling evidence for a model wherein post-translational modification enables the transition of functionally specialized condensates, highlighting a co-evolution link between CTD condensation and splicing. The C-terminal domain of the largest subunit of RNA polymerase II (CTD) is phosphorylated and recruits regulators of transcription. Here the authors show that phosphorylated CTD, upon specific binding to transcription regulators, forms distinct condensates from wildtype CTD, impact promoter binding and RNA processing.
- Subjects
RNA polymerase II; ALTERNATIVE RNA splicing; GENETIC transcription; POST-translational modification; CELL growth; RNA splicing
- Publication
Nature Communications, 2024, Vol 15, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-024-52391-6