The RNA Polymerase II CTD Kinase CTDK-I Affects Pre-mRNA 3′ Cleavage/Polyadenylation through the Processing Component Pti1p

Skaar, David; Greenleaf, Arno L.

doi:10.1016/s1097-2765(02)00731-1

Cited by 48 publications

(51 citation statements)

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“…In addition, the N-terminus and the hinge region of Pti1p interact with Glc7p [204]. Defects in Pti1p affect the cleavage site selection and the polyadenylation length of some pre-mRNAs, but the presence of Pti1p is not essential for 3′-end processing [203]. Over-expression of Pti1p prevents polyadenylation, consistent with its association with snoRNA, which are not polyadenylated.…”

Section: Pti1pmentioning

confidence: 96%

“…Pta1p purifies with CPF and can be further purified into CF II. It interacts directly with the C-terminus of Brr5p/Ysh1p [111], Cft2p/Ydh1p [118], Syc1p, Glc7p, Pti1p, Ssu72p and Swd2p [81,202,203]. Symplekin was identified through its interaction with the hinge region of CstF-64 [141], and forms a stable complex with CPSF and CstF.…”

Section: Symplekin (Pta1p)mentioning

confidence: 99%

“…It is a sequence homolog of Rna15p and CstF-64, and contains a RRM at the N-terminus (residues 20-100). The hinge region (residues 185-260) is more conserved with CstF-64 than Rna15p, and interacts with Rna14p, Pcf11p and Pta1p [203]. In addition, the N-terminus and the hinge region of Pti1p interact with Glc7p [204].…”

Section: Pti1pmentioning

confidence: 99%

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Protein factors in pre-mRNA 3′-end processing

Mandel

Bai

Tong

2007

Cell. Mol. Life Sci.

352

482

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Most eukaryotic mRNA precursors (pre-mRNAs) must undergo extensive processing, including cleavage and polyadenylation at the 3′-end. Processing at the 3′-end is controlled by sequence elements in the pre-mRNA (cis elements) as well as protein factors. Despite the seeming biochemical simplicity of the processing reactions, more than 14 proteins have been identified for the mammalian complex, and more than 20 proteins have been identified for the yeast complex. The 3′-end processing machinery also has important roles in transcription and splicing. The mammalian machinery contains several sub-complexes, including cleavage and polyadenylation specificity factor (CPSF), cleavage stimulation factor (CstF), cleavage factor I (CF I m ), and cleavage factor II (CF II m ). Additional protein factors include poly(A) polymerase (PAP), poly(A) binding protein (PABP), symplekin, and the C-terminal domain (CTD) of RNA polymerase II largest subunit. The yeast machinery includes cleavage factor IA (CF IA), cleavage factor IB (CF IB), and cleavage and polyadenylation factor (CPF).

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Section: Pti1pmentioning

confidence: 96%

Section: Symplekin (Pta1p)mentioning

confidence: 99%

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Protein factors in pre-mRNA 3′-end processing

Mandel

Bai

Tong

2007

Cell. Mol. Life Sci.

352

482

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“…Just as capping enzyme recruitment attends CTD phosphorylation by Kin28, the recruitment of factors involved in elongation and RNA processing is considered to be one consequence of CTD phosphorylation by [33][34][35][36]. Consistent with this, CTK1, encoding the catalytic subunit of CTDK-I, has been found to interact genetically with several of these factors (19)(20)(21)35).A growing body of evidence also suggests that the role of CTD phosphorylation is not confined to recruiting factors that mediate mRNA maturation. For example, CTD phosphorylation by CTDK-I also plays a role in recruiting the histone H3 Lys36 methyltransferase Set2, and ctk1Δ cells are defective for histone H3 Lys36 methylation (37,38).…”

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Expanding the Functional Repertoire of CTD Kinase I and RNA Polymerase II: Novel PhosphoCTD-Associating Proteins in the Yeast Proteome

2004

Self Cite

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CTD kinase I (CTDK-I) of Saccharomyces cerevisiae is required for normal phosphorylation of the C-terminal repeat domain (CTD) on elongating RNA polymerase II. To elucidate cellular roles played by this kinase and the hyperphosphorylated CTD (phosphoCTD) it generates, we systematically searched yeast extracts for proteins that bound to the phosphoCTD made by CTDK-I in vitro. Initially, using a combination of far-western blotting and phosphoCTD affinity chromatography, we discovered a set of novel phosphoCTD-associating proteins (PCAPs) implicated in a variety of nuclear functions. We identified the phosphoCTD-interacting domains of a number of these PCAPs, and in several test cases (namely, Set2, Ssd1, and Hrr25) adduced evidence that phosphoCTD binding is functionally important in vivo. Employing surface plasmon resonance (BIACORE) analysis, we found that recombinant versions of these and other PCAPs bind preferentially to CTD repeat peptides carrying SerPO 4 residues at positions 2 and 5 of each seven amino acid repeat, consistent with the positional specificity of CTDK-I in vitro [Jones, J. C., et al. (2004) J. Biol. Chem. 279, 24957-24964]. Subsequently, we used a synthetic CTD peptide with three doubly phosphorylated repeats (2,5P) as an affinity matrix, greatly expanding our search for PCAPs. This resulted in identification of approximately 100 PCAPs and associated proteins representing a wide range of functions (e.g., transcription, RNA processing, chromatin structure, DNA metabolism, protein synthesis and turnover, RNA degradation, snRNA modification, and snoRNP biogenesis). The varied nature of these PCAPs and associated proteins points to an unexpectedly diverse set of connections between Pol II elongation and other processes, conceptually expanding the role played by CTD phosphorylation in functional organization of the nucleus.The carboxyl-terminal repeat domain (CTD) 1 of the largest subunit of eukaryotic RNA polymerase II (Pol II) comprises tandem repeats of the consensus heptapeptide YSPTSPS. This highly conserved sequence, which is repeated 26 times in yeast and 52 times in mammals, is essential for viability. Phosphorylation of the CTD regulates the activities of the polymerase: only Pol II with an unphosphorylated CTD (Pol IIA) is thought to be able to assemble into preinitiation complexes at the promoter, whereas elongating polymerase has a hyperphosphorylated CTD (Pol IIO) (1,2). The serines at positions 2 and 5 within the heptad repeat represent major sites of phosphorylation during transcription. † Supported by National Institutes of Health Grant GM40505.© 2004 American Chemical Society * To whom correspondence should be addressed. . E-mail: arno@biochem.duke.edu. 1 Abbreviations: CTDK-I, CTD kinase I; Pol II, RNA polymerase II; CTD, C-terminal repeat domain; phosphoCTD, hyperphosphorylated CTD; PCTD, phosphoCTD; PCAP, phosphoCTD-associating protein; PCID, phosphoCTD-interacting domain; SGD, Saccharomyces Genome Database; SPR, surface plasmon resonance; RU, response units. NIH Publi...

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“…Like capping, pol II CTD can play an important role in splicing by regulating the efficiency and specificity of splicing as well as recruiting the machinery. However, the functional specificity of the two different serines is unknown.Similar to splicing, the 3'-end processing of mRNA is affected in cells through a deletion of the pol II CTD or a loss of CTD phosphorylation, even though nascent RNA carries the consensus recognition sites (Fong and Bentley, 2001;Proudfoot et al, 2002;Skaar and Greenleaf, 2002;Ahn et al, 2004). 3'-end modifications of the pre-mRNA proceeds through two steps; endonucleolytic cleavage of the 250 Exp.…”

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confidence: 99%

RNA polymerase II carboxy-terminal domain with multiple connections

Cho¹

2007

Exp Mol Med

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The largest subunit of eukaryotic RNA polymerase II contains a unique domain at its carboxy-terminus, which is referred to as the carboxy-terminal domain (CTD). The CTD is made up of an evolutionarily conserved heptapeptide repeat (YSPTSPS). Over the past decade, there has been increasing attention on the role of the CTD in transcription regulation in the view of mRNA processing and chromatin remodeling. This paper provides a brief overview of the recent progress in the dynamic changes in CTD phosphorylation and its role in integrating multiple nuclear events.Keywords: carboxy-terminal domain kinase; chromatin; phosphorylation; histones; RNA polymerase II; RNA processing, post-transcriptional IntroductionThe largest subunit of eukaryotic RNA polymerase II (pol II) carboxy-terminal domain (CTD) consists of conserved heptapeptide repeats (Y 1 S 2 P 3 T 4 S 5 P 6 S 7 ) (Dahmus, 1996). Mammalian pol II CTD contains 52 repeats, whereas the yeast Saccharomyces cerevisiae CTD has 26-27. A deletion of the mouse, Drosophila, or yeast CTD is lethal. Therefore, the CTD is essential for the viability of an organism, even though the number of repeats can be reduced.Partial deletions of the CTD result in reduced transcription in vivo, and defective responses to various activators. The CTD acts as a platform to couple the mRNA metabolism and chromatin function to the transcription as it recruits various RNA processing/export and histone modifying factors to the transcription complex (Bentley, 2005;Buratowski, 2005;Phatnani and Greenleaf, 2006). This means that the CTD is very important for organizing various nuclear functions to acquire the proper regulation of gene expression. Those functions often depend on the CTD modification such as phosphorylation. Indeed, the CTD is rich in phosphoacceptor amino acid residues and undergoes reversible phosphorylation during the transcription cycle. Two forms of RNA pol II, which differ in the level of phosphorylation of the CTD, can be distinguished and are believed to have distinct functions in the transcription cycle; RNA pol IIa, with a hypophosphorylated CTD, is the form that assembles into the transcription initiation complexes, whereas pol IIo, with a hyperphosphorylated CTD is associated with the transcription elongation complexes. Phosphorylation occurs mainly at discrete serines (S) within the CTD repeats (S2, S5), which is then recognized by different proteins that interconnect the transcription to various nuclear metabolisms. Accordingly, serine phosphorylation is known as the 'CTD code', in a similar way that the 'histone code' refers to the histone modification (Buratowski, 2003). CTD with the phosphorylation codeEarlier models based on a two-step transcription cycle, in which pol IIa was assembled at the promoter and pol IIo carried out transcription elongation, have evolved to one with a more complex CTD phosphorylation cycle. Different modified forms of pol II dominate different stages of transcription (Komarnisky et al., 2000). Pol II assembled at the promoter is...

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The RNA Polymerase II CTD Kinase CTDK-I Affects Pre-mRNA 3′ Cleavage/Polyadenylation through the Processing Component Pti1p

Cited by 48 publications

References 53 publications

Protein factors in pre-mRNA 3′-end processing

Protein factors in pre-mRNA 3′-end processing

Expanding the Functional Repertoire of CTD Kinase I and RNA Polymerase II: Novel PhosphoCTD-Associating Proteins in the Yeast Proteome

RNA polymerase II carboxy-terminal domain with multiple connections

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