ArticleMolecular and cellular biology2013
Trypanosome cdc2-related kinase 9 controls spliced leader RNA cap4 methylation and phosphorylation of RNA polymerase II subunit RPB1.
Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 34 citations in OpenAlex.
- Article
- SF3B1 phosphorylation is an evolutionarily conserved step in spliceosome activation carried out by the divergent, OTS964-insensitive kinase CRK9 in trypanosomes.Nucleic acids research · 2026Article
- Chemical genetics reveals Leishmania KKT2 and CRK9 kinase activity is required for cell cycle progression.PLoS pathogens · 2026Article
- Structural basis of Spliced Leader RNA recognition by the Trypanosoma brucei cap-binding complex.Nature communications · 2025Article
- CDK7 and CDK9 inhibition interferes with transcription, translation, and stemness, and induces cytotoxicity in GBM irrespective of temozolomide sensitivity.Neuro-oncology · 2024Article
- Knockout of protein phosphatase 1 in Leishmania major reveals its role during RNA polymerase II transcription termination.Nucleic acids research · 2023Article
- Distinguishing functions of trypanosomatid protein kinases.Trends in parasitology · 2022Review
- Promastigote-to-Amastigote Conversion inPathogens (Basel, Switzerland) · 2022Review
- A distinct complex of PRP19-related and trypanosomatid-specific proteins is required for pre-mRNA splicing in trypanosomes.Nucleic acids research · 2021Article
- Nuclear mRNA maturation and mRNA export control: from trypanosomes to opisthokonts.Parasitology · 2021Review
- A nuclear enterprise: zooming in on nuclear organization and gene expression control in the African trypanosome.Parasitology · 2021Review
- The CRK2-CYC13 complex functions as an S-phase cyclin-dependent kinase to promote DNA replication in Trypanosoma brucei.BMC biology · 2021Article
- Rapid block of pre-mRNA splicing by chemical inhibition of analog-sensitive CRK9 in Trypanosoma brucei.Molecular microbiology · 2020Article
- Regulation of gene expression in trypanosomatids: living with polycistronic transcription.Open biology · 2019Article
- Nuclear Phosphatidylinositol 5-Phosphatase Is Essential for Allelic Exclusion of Variant Surface Glycoprotein Genes in Trypanosomes.Molecular and cellular biology · 2019Article
- An RNA polymerase II-associated TFIIF-like complex is indispensable for SL RNA gene transcription in Trypanosoma brucei.Nucleic acids research · 2018Article
- An essential domain of an early-diverged RNA polymerase II functions to accurately decode a primitive chromatin landscape.Nucleic acids research · 2017Article
- Cyclin-Dependent Kinase CRK9, Required for Spliced Leader trans Splicing of Pre-mRNA in Trypanosomes, Functions in a Complex with a New L-Type Cyclin and a Kinetoplastid-Specific Protein.PLoS pathogens · 2016Article
- The spliceosomal PRP19 complex of trypanosomes.Molecular microbiology · 2015Article
- Kinases as druggable targets in trypanosomatid protozoan parasites.Chemical reviews · 2014Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Conserved from yeast to mammals, phosphorylation of the heptad repeat sequence Tyr(1)-Ser(2)-Pro(3)-Thr(4)-Ser(5)-Pro(6)-Ser(7) in the carboxy-terminal domain (CTD) of the largest RNA polymerase II (RNA Pol II) subunit, RPB1, mediates the enzyme's promoter escape and binding of RNA-processing factors, such as the m(7)G capping enzymes. The first critical step, Ser(5) phosphorylation, is carried out by cyclin-dependent kinase 7 (CDK7), a subunit of the basal transcription factor TFIIH. Many early-diverged protists, such as the lethal human parasite Trypanosoma brucei, however, lack the heptad repeats and, apparently, a CDK7 ortholog. Accordingly, characterization of trypanosome TFIIH did not identify a kinase component. The T. brucei CTD, however, is phosphorylated and essential for transcription. Here we show that silencing the expression of T. brucei cdc2-related kinase 9 (CRK9) leads to a loss of RPB1 phosphorylation. Surprisingly, this event did not impair RNA Pol II transcription or cotranscriptional m(7)G capping. Instead, we observed that CRK9 silencing led to a block of spliced leader (SL) trans splicing, an essential step in trypanosome mRNA maturation, that was caused by hypomethylation of the SL RNA's unique cap4.
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