Dynamic modification of heptad-repeats with the consensus sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7 of RNA polymerase 11 (RNAPII) C-terminal domain (ctd) regulates transcription-coupled processes. Mass spectrometry ...
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Dynamic modification of heptad-repeats with the consensus sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7 of RNA polymerase 11 (RNAPII) C-terminal domain (ctd) regulates transcription-coupled processes. Mass spectrometry analysis revealed that K7-residues in non-consensus repeats of human RNAPII are modified by acetylation, or mono-, di-, and tri-methylation. K7ac, K7me2, and K7me3 were found exclusively associated with phosphorylated ctd peptides, while K7me1 occurred also in non-phosphorylated ctd. The monoclonal antibody 1F5 recognizes K7me1/2 residues in ctd and reacts with RNAPIIA. Treatment of cellular extracts with phosphatase or of cells with the kinase inhibitor flavopiridol unmasked the K7me1/2 epitope in RNAPII0, consistent with the association of K7me1/2 marks with phosphorylated ctd peptides. Genome-wide profiling revealed high levels of K7me1/2 marks at the transcriptional start site of genes for sense and antisense transcribing RNAPII. The new K7 modifications further expand the mammalian ctd code to allow regulation of differential gene expression.
Ess1 is a prolyl isomerase that regulates the structure and function of eukaryotic RNA polymerase II. Ess1 works by catalyzing the cis/trans conversion of pSer5-Pro6 bonds, and to a lesser extent pSer2-Pro3 bonds, wit...
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Ess1 is a prolyl isomerase that regulates the structure and function of eukaryotic RNA polymerase II. Ess1 works by catalyzing the cis/trans conversion of pSer5-Pro6 bonds, and to a lesser extent pSer2-Pro3 bonds, within the carboxy-terminal domain (ctd) of Rpb1, the largest subunit of RNA pol II. Ess1 is conserved in organisms ranging from yeast to humans. In budding yeast, Ess1 is essential for growth and is required for efficient transcription initiation and termination, RNA processing, and suppression of cryptic transcription. In mammals, Ess1 (called Pin1) functions in a variety of pathways, including transcription, but it is not essential. Recent work has shown that Ess1 coordinates the binding and release of ctd-binding proteins that function as co-factors in the RNA pol II complex. In this way, Ess1 plays an integral role in writing (and reading) the so-called CID code to promote production of mature RNA pol II transcripts including non-coding RNAs and mRNAs. (C) 2014 Elsevier B.V. All rights reserved.
The cyclin-dependent kinases (Cdks) regulate many cellular processes, including the cell cycle, neuronal development, transcription, and posttranscriptional processing. To perform their functions, Cdks bind to specifi...
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The cyclin-dependent kinases (Cdks) regulate many cellular processes, including the cell cycle, neuronal development, transcription, and posttranscriptional processing. To perform their functions, Cdks bind to specific cyclin subunits to form a functional and active cyclin/Cdk complex. This review is focused on Cyclin K, which was originally considered an alternative subunit of Cdk9, and on its newly identified partners, Cdk12 and Cdk13. We briefly summarize research devoted to each of these proteins. We also discuss the proteins' functions in the regulation of gene expression via the phosphorylation of serine 2 in the C-terminal domain of RNA polymerase II, contributions to the maintenance of genome stability, and roles in the onset of human disease and embryo development.
In eukaryotic cells, the transcription of genes is accurately orchestrated both spatially and temporally by the C-terminal domain of RNA polymerase II (ctd). The ctd provides a dynamic platform to recruit different re...
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In eukaryotic cells, the transcription of genes is accurately orchestrated both spatially and temporally by the C-terminal domain of RNA polymerase II (ctd). The ctd provides a dynamic platform to recruit different regulators of the transcription apparatus. Different posttranslational modifications are precisely applied to specific sites of the ctd to coordinate transcription process. Regulators of the RNA polymerase II must identify specific sites in the ctd for cellular survival, metabolism, and development. Even though the ctd is disordered in the eukaryotic RNA polymerase II crystal structures due to its intrinsic flexibility, recent advances in the complex structural analysis of the ctd with its binding partners provide essential clues for understanding how selectivity is achieved for individual site recognition. The recent discoveries of the interactions between the ctd and histone modification enzymes disclose an important role of the ctd in epigenetic control of the eukaryotic gene expression. The intersection of the ctd code with the histone code discloses an intriguing yet complicated network for eukaryotic transcriptional regulation.
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