ArticleGenes & development2016
P-TEFb regulation of transcription termination factor Xrn2 revealed by a chemical genetic screen for Cdk9 substrates.
Article in Genes & development, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 1 of them a synthesis that pooled it.
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Who cites it
104 citing papers in PubMed, 1 synthesis or guideline pooled it, 137 citations in OpenAlex.
- Meta-analysis of cellular phosphoproteome datasets exploring phospho-signaling associated with the RNA-binding protein RAVER1.Scientific reports · 2026Pooled it
- CDK2/9 blockade remodels chromatin and drives phenotypic plasticity in glioblastoma organoids.Cell communication and signaling : CCS · 2026Article
- Structural basis for P-TEFb association with BRD4.bioRxiv : the preprint server for biology · 2026Article
- Targeting CDKs in the RNAPII transcription cycle.Nature reviews. Drug discovery · 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
- The Promoter-Proximal Pause: A Decision Point Governing RNA Polymerase II Fate.Annual review of biochemistry · 2026Review
- ELOF1 is a core component of the promoter-proximal paused RNA polymerase II complex.bioRxiv : the preprint server for biology · 2026Article
- NELF prevents transcriptional readthrough into DNA replication zones in cancer cells.EMBO reports · 2026Article
- Phosphorylation of SF3B1 by CDK11 orchestrates spliceosome activation via SNIP1-dependent RES complex recruitment.Nature communications · 2026Article
- SF3B1 Phosphorylation Prompts U2AF2 Dissociation for Widespread Control of pre-mRNA Splicing.bioRxiv : the preprint server for biology · 2026Article
- Histone H2B monoubiquitylation regulates elongation-to-termination transition in RNA polymerase II transcription.Communications biology · 2025Article
- Base Composition Influences the Position and Precision of RNA Polymerase II Disassociation in Basal and Perturbed Conditions.bioRxiv : the preprint server for biology · 2025Article
- Transcription quality control at the promoter-proximal checkpoint.Genes & development · 2025Review
- Transcriptional pause release at enhancers mediates cell identity.NAR cancer · 2025Review
- CDK7-CDK11 axis in spliceosome regulation and pre-mRNA splicing.Nucleic acids research · 2025Article
- DSS1 is required for proper Integrator-PP2A function.Nature communications · 2025Article
- Regulation of RNA polymerase II transcription through re-initiation and bursting.Molecular cell · 2025Review
- Tripartite phosphorylation of SPT5 by CDK9 times pause release and tunes elongation rate of RNA polymerase II.Molecular cell · 2025Article
- ZmSSRP1 facilitates the progression of RNA polymerase II and is essential for kernel development in maize.The Plant cell · 2025Article
44 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 7 institutions in 2 countries.
Funding
Abstract
The transcription cycle of RNA polymerase II (Pol II) is regulated at discrete transition points by cyclin-dependent kinases (CDKs). Positive transcription elongation factor b (P-TEFb), a complex of Cdk9 and cyclin T1, promotes release of paused Pol II into elongation, but the precise mechanisms and targets of Cdk9 action remain largely unknown. Here, by a chemical genetic strategy, we identified ∼ 100 putative substrates of human P-TEFb, which were enriched for proteins implicated in transcription and RNA catabolism. Among the RNA processing factors phosphorylated by Cdk9 was the 5'-to-3' "torpedo" exoribonuclease Xrn2, required in transcription termination by Pol II, which we validated as a bona fide P-TEFb substrate in vivo and in vitro. Phosphorylation by Cdk9 or phosphomimetic substitution of its target residue, Thr439, enhanced enzymatic activity of Xrn2 on synthetic substrates in vitro. Conversely, inhibition or depletion of Cdk9 or mutation of Xrn2-Thr439 to a nonphosphorylatable Ala residue caused phenotypes consistent with inefficient termination in human cells: impaired Xrn2 chromatin localization and increased readthrough transcription of endogenous genes. Therefore, in addition to its role in elongation, P-TEFb regulates termination by promoting chromatin recruitment and activation of a cotranscriptional RNA processing enzyme, Xrn2.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.