ArticleMolecular cell2016
Engineered Covalent Inactivation of TFIIH-Kinase Reveals an Elongation Checkpoint and Results in Widespread mRNA Stabilization.
Article in Molecular cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed.
- Article
- Multi-omics and biochemical reconstitution reveal CDK7-dependent mechanisms controlling RNA polymerase II function at gene 5'- and 3' ends.Cell reports · 2025Article
- Decay drives RNA abundance regulation using three distinct regulatory mechanisms.bioRxiv : the preprint server for biology · 2025Article
- Chromatin endogenous cleavage provides a global view of yeast RNA polymerase II transcription kinetics.eLife · 2024Article
- Chromatin endogenous cleavage provides a global view of yeast RNA polymerase II transcription kinetics.bioRxiv : the preprint server for biology · 2024Article
- The general transcription factors (GTFs) of RNA polymerase II and their roles in plant development and stress responses.Critical reviews in biochemistry and molecular biology · 2024Review
- Multiple direct and indirect roles of the Paf1 complex in transcription elongation, splicing, and histone modifications.Cell reports · 2024Article
- Homeostasis of mRNA concentrations through coupling transcription, export, and degradation.iScience · 2024Article
- Multiple direct and indirect roles of Paf1C in elongation, splicing, and histone post-translational modifications.bioRxiv : the preprint server for biology · 2024Article
- Small molecule inhibitors of transcriptional cyclin-dependent kinases impose HIV-1 latency, presenting "block and lock" treatment strategies.Antimicrobial agents and chemotherapy · 2024Article
- Coordination of rhythmic RNA synthesis and degradation orchestrates 24- and 12-h RNA expression patterns in mouse fibroblasts.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Coordination of rhythmic RNA synthesis and degradation orchestrates 24-hour and 12-hour RNA expression patterns in mouse fibroblasts.bioRxiv : the preprint server for biology · 2023Article
- Systematic Design of Adenosine Analogs as Inhibitors of aJournal of medicinal chemistry · 2023Article
- Sumoylation is Largely Dispensable for Normal Growth but Facilitates Heat Tolerance in Yeast.Molecular and cellular biology · 2023Article
- An integrated SAGA and TFIID PIC assembly pathway selective for poised and induced promoters.Genes & development · 2022Article
- Mpe1 senses the binding of pre-mRNA and controls 3' end processing by CPF.Molecular cell · 2022Article
- Transcription feedback dynamics in the wake of cytoplasmic mRNA degradation shutdown.Nucleic acids research · 2022Article
- CDK12 Is Necessary to Promote Epidermal Differentiation Through Transcription Elongation.Stem cells (Dayton, Ohio) · 2022Article
- Functional interaction between the RNA exosome and the sirtuin deacetylase Hst3 maintains transcriptional homeostasis.Genes & development · 2022Article
- Spatiotemporal coordination of transcription preinitiation complex assembly in live cells.Molecular cell · 2021Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
During transcription initiation, the TFIIH-kinase Kin28/Cdk7 marks RNA polymerase II (Pol II) by phosphorylating the C-terminal domain (CTD) of its largest subunit. Here we describe a structure-guided chemical approach to covalently and specifically inactivate Kin28 kinase activity in vivo. This method of irreversible inactivation recapitulates both the lethal phenotype and the key molecular signatures that result from genetically disrupting Kin28 function in vivo. Inactivating Kin28 impacts promoter release to differing degrees and reveals a "checkpoint" during the transition to productive elongation. While promoter-proximal pausing is not observed in budding yeast, inhibition of Kin28 attenuates elongation-licensing signals, resulting in Pol II accumulation at the +2 nucleosome and reduced transition to productive elongation. Furthermore, upon inhibition, global stabilization of mRNA masks different degrees of reduction in nascent transcription. This study resolves long-standing controversies on the role of Kin28 in transcription and provides a rational approach to irreversibly inhibit other kinases in vivo.
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