scholarly journals Human cap methyltransferase (RNMT) N-terminal non-catalytic domain mediates recruitment to transcription initiation sites

2013 ◽  
Vol 455 (1) ◽  
pp. 67-73 ◽  
Author(s):  
Michael Aregger ◽  
Victoria H. Cowling
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Translation Initiation ◽  
Transcription Initiation ◽  
Catalytic Domain ◽  
Terminal Domain

The mRNA methyl cap recruits the mediators of processing events and translation initiation. We report that RNMT, the human cap methyltransferase, is recruited to RNA polymerase II via the N-terminal domain and is required for gene expression and cell proliferation.

Crystal structure of Ssu72, an essential eukaryotic phosphatase specific for the C-terminal domain of RNA polymerase II, in complex with a transition state analogue

2011 ◽  
Vol 434 (3) ◽  
pp. 435-444 ◽  
Author(s):  
Yong Zhang ◽  
Mengmeng Zhang ◽  
Yan Zhang
Keyword(s):  
Rna Polymerase ◽  
Transition State ◽  
Rna Polymerase Ii ◽  
Transcription Initiation ◽  
Complex Structure ◽  
Protein Tyrosine Phosphatases ◽  
Cysteine Residue ◽  
Phosphoryl Transfer ◽  
Terminal Domain ◽  
Deep Groove

Reversible phosphorylation of the CTD (C-terminal domain) of the eukaryotic RNA polymerase II largest subunit represents a critical regulatory mechanism during the transcription cycle and mRNA processing. Ssu72 is an essential phosphatase conserved in eukaryotes that dephosphorylates phosphorylated Ser5 of the CTD heptapeptide. Its function is implicated in transcription initiation, elongation and termination, as well as RNA processing. In the present paper we report the high resolution X-ray crystal structures of Drosophila melanogaster Ssu72 phosphatase in the apo form and in complex with an inhibitor mimicking the transition state of phosphoryl transfer. Ssu72 facilitates dephosphorylation of the substrate through a phosphoryl-enzyme intermediate, as visualized in the complex structure of Ssu72 with the oxo-anion compound inhibitor vanadate at a 2.35 Å (1 Å=0.1 nm) resolution. The structure resembles the transition state of the phosphoryl transfer with vanadate exhibiting a trigonal bi-pyramidal geometry covalently bonded to the nucleophilic cysteine residue. Interestingly, the incorporation of oxo-anion compounds greatly stabilizes a flexible loop containing the general acid, as detected by an increase of melting temperature of Ssu72 detected by differential scanning fluorimetry. The Ssu72 structure exhibits a core fold with a similar topology to that of LMWPTPs [low-molecular-mass PTPs (protein tyrosine phosphatases)], but with an insertion of a unique ‘cap’ domain to shelter the active site from the solvent with a deep groove in between where the CTD substrates bind. Mutagenesis studies in this groove established the functional roles of five residues (Met17, Pro46, Asp51, Tyr77 and Met85) that are essential specifically for substrate recognition.

Transcription initiation complexes and upstream activation with RNA polymerase II lacking the C-terminal domain of the largest subunit

1990 ◽  
Vol 10 (10) ◽  
pp. 5562-5564
Author(s):  
S Buratowski ◽  
P A Sharp
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Transcription Initiation ◽  
Adenovirus Type ◽  
Late Promoter ◽  
Terminal Domain ◽  
Late Transcription ◽  
Major Late Promoter

RNA polymerase II assembles with other factors on the adenovirus type 2 major late promoter to generate pairs of transcription initiation complexes resolvable by nondenaturing gel electrophoresis. The pairing of the complexes is caused by the presence or absence of the C-terminal domain of the largest subunit. This domain is not required for transcription stimulation by the major late transcription factor in vitro.

scholarly journals The Myc Transactivation Domain Promotes Global Phosphorylation of the RNA Polymerase II Carboxy-Terminal Domain Independently of Direct DNA Binding

2007 ◽  
Vol 27 (6) ◽  
pp. 2059-2073 ◽  
Author(s):  
Victoria H. Cowling ◽  
Michael D. Cole
Keyword(s):  
Dna Binding ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Transcription Initiation ◽  
Target Genes ◽  
Dependent Manner ◽  
Transactivation Domain ◽  
Pol Ii ◽  
Terminal Domain ◽  
Ctd Phosphorylation

ABSTRACT Myc is a transcription factor which is dependent on its DNA binding domain for transcriptional regulation of target genes. Here, we report the surprising finding that Myc mutants devoid of direct DNA binding activity and Myc target gene regulation can rescue a substantial fraction of the growth defect in myc −/− fibroblasts. Expression of the Myc transactivation domain alone induces a transcription-independent elevation of the RNA polymerase II (Pol II) C-terminal domain (CTD) kinases cyclin-dependent kinase 7 (CDK7) and CDK9 and a global increase in CTD phosphorylation. The Myc transactivation domain binds to the transcription initiation sites of these promoters and stimulates TFIIH binding in an MBII-dependent manner. Expression of the Myc transactivation domain increases CDK mRNA cap methylation, polysome loading, and the rate of translation. We find that some traditional Myc transcriptional target genes are also regulated by this Myc-driven translation mechanism. We propose that Myc transactivation domain-driven RNA Pol II CTD phosphorylation has broad effects on both transcription and mRNA metabolism.

scholarly journals A three-step pathway of transcription initiation leading to promoter clearance at an activation RNA polymerase II promoter.

1996 ◽  
Vol 16 (4) ◽  
pp. 1614-1621 ◽  
Author(s):  
Y Jiang ◽  
M Yan ◽  
J D Gralla
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Transcription Initiation ◽  
Potential Effect ◽  
Multiple Roles ◽  
Elongation Complex ◽  
Terminal Domain ◽  
Step Model ◽  
Dna Strands

The progress of transcription bubbles during inhibition in vitro was followed in order to learn how RNA polymerase II begins transcription at the activated adenovirus E4 promoter. The issues addressed include the multiple roles of ATP, the potential effect of polymerase C-terminal domain phosphorylation, and the ability of polymerase to clear the promoter for reinitiation. The results lead to a three-step model for the transition from closed complex to elongation complex, two steps of which use ATP independently. In the first step, studied previously, ATP is hydrolyzed to open the DNA strands over the start site. In a second step, apparently independent of ATP, transcription bubbles move into the initial transcribed region where RNA synthesis can stall. In the third step, transcripts can be made as polymerase is released from these stalled positions with the assistance of an ATP-dependent process, likely phosphorylation of the polymerase C-terminal domain. After this third step, the promoter becomes cleared, allowing for the reinitiation of transcription.

Gene insulation. Part I: natural strategies in yeast and Drosophila

2010 ◽  
Vol 88 (6) ◽  
pp. 875-884 ◽  
Author(s):  
Michèle Amouyal
Keyword(s):  
Gene Expression ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Transcription Initiation ◽  
Rna Polymerase Iii ◽  
Eukaryotic Cells ◽  
Trna Genes ◽  
Initiation Complex ◽  
Heterochromatin Formation ◽  
Transcription Initiation Complex

This review in two parts deals with the increasing number of processes known to be used by eukaryotic cells to protect gene expression from undesired genomic enhancer or chromatin effects, by means of the so-called insulators or barriers. The most advanced studies in this expanding field concern yeasts and Drosophila (this article) and the vertebrates (next article in this issue). Clearly, the cell makes use of every gene context to find the appropriate, economic, solution. Thus, besides the elements formerly identified and specifically dedicated to insulation, a number of unexpected elements are diverted from their usual function to structure the genome and enhancer action or to prevent heterochromatin spreading. They are, for instance, genes actively transcribed by RNA polymerase II or III, partial elements of these transcriptional machineries (stalled RNA polymerase II, normally required by genes that must respond quickly to stimuli, or TFIIIC bound at its B-box, normally required by RNA polymerase III for assembly of the transcription initiation complex at tRNA genes), or genomic sequences occupied by variants of standard histones, which, being rapidly and permanently replaced, impede heterochromatin formation.

scholarly journals Quantitative modelling predicts the impact of DNA methylation on RNA polymerase II traffic

2019 ◽  
Vol 116 (30) ◽  
pp. 14995-15000 ◽  
Author(s):  
Justyna Cholewa-Waclaw ◽  
Ruth Shah ◽  
Shaun Webb ◽  
Kashyap Chhatbar ◽  
Bernard Ramsahoye ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Rett Syndrome ◽  
Transcription Initiation ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
A Genome ◽  
The Impact

Patterns of gene expression are primarily determined by proteins that locally enhance or repress transcription. While many transcription factors target a restricted number of genes, others appear to modulate transcription levels globally. An example is MeCP2, an abundant methylated-DNA binding protein that is mutated in the neurological disorder Rett syndrome. Despite much research, the molecular mechanism by which MeCP2 regulates gene expression is not fully resolved. Here, we integrate quantitative, multidimensional experimental analysis and mathematical modeling to indicate that MeCP2 is a global transcriptional regulator whose binding to DNA creates “slow sites” in gene bodies. We hypothesize that waves of slowed-down RNA polymerase II formed behind these sites travel backward and indirectly affect initiation, reminiscent of defect-induced shockwaves in nonequilibrium physics transport models. This mechanism differs from conventional gene-regulation mechanisms, which often involve direct modulation of transcription initiation. Our findings point to a genome-wide function of DNA methylation that may account for the reversibility of Rett syndrome in mice. Moreover, our combined theoretical and experimental approach provides a general method for understanding how global gene-expression patterns are choreographed.

scholarly journals Plasmodium falciparum var gene expression is developmentally controlled at the level of RNA polymerase II‐mediated transcription initiation

2007 ◽  
Vol 63 (4) ◽  
pp. 1237-1247 ◽  
Author(s):  
Sue Kyes ◽  
Zóe Christodoulou ◽  
Robert Pinches ◽  
Neline Kriek ◽  
Paul Horrocks ◽  
...  
Keyword(s):  
Gene Expression ◽  
Plasmodium Falciparum ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Transcription Initiation ◽  
Var Gene
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