Structure of Ctk3, a subunit of the RNA polymerase II CTD kinase complex, reveals a noncanonical CTD-interacting domain fold

Mühlbacher, Wolfgang; Mayer, Andreas; Sun, Mai; Remmert, Michael; Cheung, Alan C. M.; Niesser, Jürgen; Soeding, Johannes; Cramer, Patrick

doi:10.1002/prot.24869

Cited by 5 publications

(2 citation statements)

References 60 publications

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“…To investigate this in vitro, we prepared one EF complex in recombinant form. We chose the prominent Ser2 kinase complex CTDK-I that comprises Ctk1, Ctk2, and the small subunit Ctk3 (Mühlbacher et al, 2015; Sterner et al, 1995). CTDK-I is the main yeast kinase responsible for phosphorylating the Pol II CTD at Ser2 (Patturajan et al, 1999; Cho et al, 2001), and this is a decisive event in establishing a mature Pol II elongation complex.…”

Section: Resultsmentioning

confidence: 99%

RNA-dependent chromatin association of transcription elongation factors and Pol II CTD kinases

Battaglia

Lidschreiber

Baejen

et al. 2017

eLife

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For transcription through chromatin, RNA polymerase (Pol) II associates with elongation factors (EFs). Here we show that many EFs crosslink to RNA emerging from transcribing Pol II in the yeast Saccharomyces cerevisiae. Most EFs crosslink preferentially to mRNAs, rather than unstable non-coding RNAs. RNA contributes to chromatin association of many EFs, including the Pol II serine 2 kinases Ctk1 and Bur1 and the histone H3 methyltransferases Set1 and Set2. The Ctk1 kinase complex binds RNA in vitro, consistent with direct EF-RNA interaction. Set1 recruitment to genes in vivo depends on its RNA recognition motifs (RRMs). These results strongly suggest that nascent RNA contributes to EF recruitment to transcribing Pol II. We propose that EF-RNA interactions facilitate assembly of the elongation complex on transcribed genes when RNA emerges from Pol II, and that loss of EF-RNA interactions upon RNA cleavage at the polyadenylation site triggers disassembly of the elongation complex.DOI: http://dx.doi.org/10.7554/eLife.25637.001

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Section: Resultsmentioning

confidence: 99%

RNA-dependent chromatin association of transcription elongation factors and Pol II CTD kinases

Battaglia

Lidschreiber

Baejen

et al. 2017

eLife

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“…Intriguingly, both Ctk2 and Ctk3 regulatory subunits are suggested to be required for activating the Ctk1 kinase (9). Thus far, the only structural information about CTDK-1 comes from the crystal structure of the Schizosaccharomyces pombe Ctk3 (Lsg1) N-terminal domain (10), which resembles other known CTD-interaction domains (CIDs). However, it is not known how the CTDK-1 complex is assembled or importantly how Ctk1 is activated by both Ctk2 and Ctk3.…”

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confidence: 99%

Structure and activation mechanism of the yeast RNA Pol II CTD kinase CTDK-1 complex

Xie

Lord

Clarke

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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The C-terminal domain (CTD) kinase I (CTDK-1) complex is the primary RNA Polymerase II (Pol II) CTD Ser2 kinase in budding yeast. CTDK-1 consists of a cyclin-dependent kinase (CDK) Ctk1, a cyclin Ctk2, and a unique subunit Ctk3 required for CTDK-1 activity. Here, we present a crystal structure of CTDK-1 at 1.85-Å resolution. The structure reveals that, compared to the canonical two-component CDK-cyclin system, the third component Ctk3 of CTDK-1 plays a critical role in Ctk1 activation by stabilizing a key element of CDK regulation, the T-loop, in an active conformation. In addition, Ctk3 contributes to the assembly of CTDK-1 through extensive interactions with both Ctk1 and Ctk2. We also demonstrate that CTDK-1 physically and genetically interacts with the serine/arginine-like protein Gbp2. Together, the data in our work reveal a regulatory mechanism of CDK complexes.

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Polyadenylation site selection: linking transcription and RNA processing via a conserved carboxy-terminal domain (CTD)-interacting protein

2016

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Despite the fact that the process of mRNA polyadenylation has been known for more than 40 years, a detailed understating of the mechanism underlying polyadenylation site selection is still far from complete. As 3' end processing is intimately associated with RNA polymerase II (RNAPII) transcription, factors that can successively interact with the transcription machinery and recognize cis-acting sequences on the nascent pre-mRNA would be well suited to contribute to poly(A) site selection. Studies using the fission yeast Schizosaccharomyces pombe have recently identified Seb1, a protein that shares homology with Saccharomyces cerevisiae Nrd1 and human SCAF4/8, and that is critical for poly(A) site selection. Seb1 binds to the C-terminal domain (CTD) of RNAPII via a conserved CTD-interaction domain and recognizes specific sequence motifs clustered downstream of the polyadenylation site on the uncleaved pre-mRNA. In this short review, we summarize insights into Seb1-dependent poly(A) site selection and discuss some unanswered questions regarding its molecular mechanism and conservation.

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Structure of Ctk3, a subunit of the RNA polymerase II CTD kinase complex, reveals a noncanonical CTD-interacting domain fold

Cited by 5 publications

References 60 publications

RNA-dependent chromatin association of transcription elongation factors and Pol II CTD kinases

RNA-dependent chromatin association of transcription elongation factors and Pol II CTD kinases

Structure and activation mechanism of the yeast RNA Pol II CTD kinase CTDK-1 complex

Polyadenylation site selection: linking transcription and RNA processing via a conserved carboxy-terminal domain (CTD)-interacting protein

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