ArticleNature communications2024
Sequence and structural determinants of RNAPII CTD phase-separation and phosphorylation by CDK7.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- RNA polymerase II phosphorylation dynamics: from molecular mechanisms to human disease.RNA biology · 2026Review
- How do low-complexity domain interactions control transcription?Biochemical Society transactions · 2026Review
- Investigating Phase Separation in Genome Folding via Multiscale Computational Modeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Residue-level mapping of crowding effects on protein phase separation.Protein science : a publication of the Protein Society · 2026Article
- RNA polymerase II: the elephant in the room.Trends in genetics : TIG · 2026Review
- The Electromechanical Connectome: Integrating Voltage, Mechanical Nano-Forces, and Subcellular Fluid Phase Dynamics in Human Neural Computation.International journal of molecular sciences · 2026Review
- Coordinating mRNA maturation: The U1 relay model.Molecular cell · 2026Review
- Distinct mechanisms of recognition of phosphorylated RNAPII C-terminal domain by BRCT repeats of the BRCA1-BARD1 complex.The Journal of biological chemistry · 2026Article
- Rational Modulation of Liquid-Liquid Phase Separation Offers Novel Ways to Combat Tauopathies.International journal of molecular sciences · 2025Review
- Off-pore Nup98 condensates mobilize heterochromatic breaks and exclude Rad51.Molecular cell · 2025Article
- Sequence and structural determinants of RNAPII CTD phase-separation and phosphorylation by CDK7.Nature communications · 2024Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
The intrinsically disordered carboxy-terminal domain (CTD) of the largest subunit of RNA Polymerase II (RNAPII) consists of multiple tandem repeats of the consensus heptapeptide Y1-S2-P3-T4-S5-P6-S7. The CTD promotes liquid-liquid phase-separation (LLPS) of RNAPII in vivo. However, understanding the role of the conserved heptad residues in LLPS is hampered by the lack of direct biochemical characterization of the CTD. Here, we generated a systematic array of CTD variants to unravel the sequence-encoded molecular grammar underlying the LLPS of the human CTD. Using in vitro experiments and molecular dynamics simulations, we report that the aromaticity of tyrosine and cis-trans isomerization of prolines govern CTD phase-separation. The cis conformation of prolines and β-turns in the SPXX motif contribute to a more compact CTD ensemble, enhancing interactions among CTD residues. We further demonstrate that prolines and tyrosine in the CTD consensus sequence are required for phosphorylation by Cyclin-dependent kinase 7 (CDK7). Under phase-separation conditions, CDK7 associates with the surface of the CTD droplets, drastically accelerating phosphorylation and promoting the release of hyperphosphorylated CTD from the droplets. Our results highlight the importance of conformationally restricted local structures within spacer regions, separating uniformly spaced tyrosine stickers of the CTD heptads, which are required for CTD phase-separation.
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