ArticleMolecular cell2025
Tripartite phosphorylation of SPT5 by CDK9 times pause release and tunes elongation rate of RNA polymerase II.
Article in Molecular cell, 2025. 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.
- Targeting CDKs in the RNAPII transcription cycle.Nature reviews. Drug discovery · 2026Review
- The Role of Transcriptional and Atypical Cyclin-Dependent Protein Kinases in Melanoma.Cancers · 2026Review
- Multisite Threonine Phosphorylation in the SPT5 C-Terminal Region 1 Enables Sequence-Dependent Regulation without Global Structural Remodeling.The journal of physical chemistry. B · 2026Article
- Mechanisms of transcription termination across the coding and noncoding loci of the genome.Nature reviews. Molecular cell biology · 2026Review
- Single-molecule imaging reveals RNA polymerase II dynamics and TAF1-dependent promoter-proximal pause release.Nature communications · 2026Article
- Glc7/PP1 triggers Paf1 complex dissociation from RNA polymerase II to enable transcription termination.Genes & development · 2026Article
- Kinetic control of mammalian transcription elongation.Nature structural & molecular biology · 2026Article
- Transcription quality control at the promoter-proximal checkpoint.Genes & development · 2025Review
- Identification and functional evaluation of cyclin-dependent kinase genes reveals that CDKB1;1 and CDKB2;2 contribute to the balance of mitosis and endoreduplication in Medicago truncatula nodule.BMC plant biology · 2025Article
- Glc7/PP1 triggers Paf1 complex dissociation from RNA polymerase II to enable transcription termination.bioRxiv : the preprint server for biology · 2025Article
- Hypoxia-mediated regulation of mRNA metabolism: from transcription to stability.Cell communication and signaling : CCS · 2025Review
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Authors and funding
2 authors.
Funding
Abstract
The RNA polymerase II (RNAPII) transcription cycle is regulated throughout its duration by protein phosphorylation. Previously, two regions phosphorylated by cyclin-dependent kinase 9 (CDK9) in elongation factor SPT5-the linker between Kyrpides-Ouzounis-Woese (KOW) x-4 and 5 domains and carboxy-terminal repeat (CTR) 1-were implicated in promoter-proximal pausing and termination, respectively. Here, we show that phosphorylations in the linker, CTR1, and a third region, CTR2, coordinately control pause release, elongation speed, and termination in HCT116 human colon cancer cells. Pausing was unaffected or increased by mutations preventing CTR1 or CTR2 phosphorylation, respectively, but attenuated when both CTRs were mutated. Whereas loss of CTR1 phosphorylation slowed elongation and repressed nascent transcription, simultaneous CTR2 mutation partially reversed both effects. Nevertheless, mutating both CTRs had additive effects on splicing, termination, steady-state mRNA levels, and cell proliferation. Therefore, tripartite SPT5 phosphorylation times pause release and tunes RNAPII elongation rate to ensure productive transcription and cell viability.
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