Structure and mechanism of RNA polymerase II CTD phosphatases.

Abstract:

:Recycling of RNA polymerase II (Pol II) after transcription requires dephosphorylation of the polymerase C-terminal domain (CTD) by the phosphatase Fcp1. We report the X-ray structure of the small CTD phosphatase Scp1, which is homologous to the Fcp1 catalytic domain. The structure shows a core fold and an active center similar to those of phosphotransferases and phosphohydrolases that solely share a DXDX(V/T) signature motif with Fcp1/Scp1. We demonstrate that the first aspartate in the signature motif undergoes metal-assisted phosphorylation during catalysis, resulting in a phosphoaspartate intermediate that was structurally mimicked with the inhibitor beryllofluoride. Specificity may result from CTD binding to a conserved hydrophobic pocket between the active site and an insertion domain that is unique to Fcp1/Scp1. Fcp1 specificity may additionally arise from phosphatase recruitment near the CTD via the Pol II subcomplex Rpb4/7, which is shown to be required for binding of Fcp1 to the polymerase in vitro.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Kamenski T,Heilmeier S,Meinhart A,Cramer P

doi

10.1016/j.molcel.2004.06.035

subject

Has Abstract

pub_date

2004-08-13 00:00:00

pages

399-407

issue

3

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(04)00380-6

journal_volume

15

pub_type

杂志文章
  • PHD3 Loss in Cancer Enables Metabolic Reliance on Fatty Acid Oxidation via Deactivation of ACC2.

    abstract::While much research has examined the use of glucose and glutamine by tumor cells, many cancers instead prefer to metabolize fats. Despite the pervasiveness of this phenotype, knowledge of pathways that drive fatty acid oxidation (FAO) in cancer is limited. Prolyl hydroxylase domain proteins hydroxylate substrate proli...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2016.08.014

    authors: German NJ,Yoon H,Yusuf RZ,Murphy JP,Finley LW,Laurent G,Haas W,Satterstrom FK,Guarnerio J,Zaganjor E,Santos D,Pandolfi PP,Beck AH,Gygi SP,Scadden DT,Kaelin WG Jr,Haigis MC

    更新日期:2016-09-15 00:00:00

  • RNA editing enzyme APOBEC1 and some of its homologs can act as DNA mutators.

    abstract::APOBEC1 is the catalytic component of an RNA editing complex but shows homology to activation-induced cytidine deaminase (AID), a protein whose function is to potentiate diversification of immunoglobulin gene DNA. Here, we show that APOBEC1 and its homologs APOBEC3C and APOBEC3G exhibit potent DNA mutator activity in ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(02)00742-6

    authors: Harris RS,Petersen-Mahrt SK,Neuberger MS

    更新日期:2002-11-01 00:00:00

  • A NASP (N1/N2)-related protein, Sim3, binds CENP-A and is required for its deposition at fission yeast centromeres.

    abstract::A defining feature of centromeres is the presence of the histone H3 variant CENP-A(Cnp1). It is not known how CENP-A(Cnp1) is specifically delivered to, and assembled into, centromeric chromatin. Through a screen for factors involved in kinetochore integrity in fission yeast, we identified Sim3. Sim3 is homologous to ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2007.10.010

    authors: Dunleavy EM,Pidoux AL,Monet M,Bonilla C,Richardson W,Hamilton GL,Ekwall K,McLaughlin PJ,Allshire RC

    更新日期:2007-12-28 00:00:00

  • Mitochondrial NAD+ Controls Nuclear ARTD1-Induced ADP-Ribosylation.

    abstract::In addition to its role as an electron transporter, mitochondrial nicotinamide adenine dinucleotide (NAD+) is an important co-factor for enzymatic reactions, including ADP-ribosylation. Although mitochondria harbor the most intra-cellular NAD+, mitochondrial ADP-ribosylation remains poorly understood. Here we provide ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2020.12.034

    authors: Hopp AK,Teloni F,Bisceglie L,Gondrand C,Raith F,Nowak K,Muskalla L,Howald A,Pedrioli PGA,Johnsson K,Altmeyer M,Pedrioli DML,Hottiger MO

    更新日期:2021-01-21 00:00:00

  • Fragile X mental retardation protein and the ribosome.

    abstract::In this issue of Molecular Cell, Chen et al. (2014) provide evidence that FMRP represses translation by binding the ribosome, suggesting a novel form of translational control. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2014.04.027

    authors: Harigaya Y,Parker R

    更新日期:2014-05-08 00:00:00

  • A Reply to "MNase-Sensitive Complexes in Yeast: Nucleosomes and Non-histone Barriers," by Chereji et al.

    abstract::In this issue of Molecular Cell, Chereji et al. (2017) present new data on MNase-sensitive particles previously identified upstream of transcription start sites at many promoters in budding yeast, and they argue, based upon negative histone-ChIP results, that they are non-nucleosomal signals generated by transcription...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2017.01.010

    authors: Kubik S,Bruzzone MJ,Albert B,Shore D

    更新日期:2017-02-02 00:00:00

  • Mouse Lefty2 and zebrafish antivin are feedback inhibitors of nodal signaling during vertebrate gastrulation.

    abstract::Mammalian lefty and zebrafish antivin form a subgroup of the TGF beta superfamily. We report that mouse mutants for lefty2 have an expanded primitive streak and form excess mesoderm, a phenotype opposite to that of mutants for the TGF beta gene nodal. Analogously, overexpression of Antivin or Lefty2 in zebrafish embry...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(00)80331-7

    authors: Meno C,Gritsman K,Ohishi S,Ohfuji Y,Heckscher E,Mochida K,Shimono A,Kondoh H,Talbot WS,Robertson EJ,Schier AF,Hamada H

    更新日期:1999-09-01 00:00:00

  • RabGDI displacement by DrrA from Legionella is a consequence of its guanine nucleotide exchange activity.

    abstract::Prenylated Rab proteins exist in the cytosol as soluble, high-affinity complexes with GDI that need to be disrupted for membrane attachment and targeting of Rab proteins. The Legionella pneumophila protein DrrA displaces GDI from Rab1:GDI complexes, incorporating Rab1 into Legionella-containing vacuoles and activating...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2009.11.014

    authors: Schoebel S,Oesterlin LK,Blankenfeldt W,Goody RS,Itzen A

    更新日期:2009-12-25 00:00:00

  • Quantifying ubiquitin signaling.

    abstract::Ubiquitin (UB)-driven signaling systems permeate biology, and are often integrated with other types of post-translational modifications (PTMs), including phosphorylation. Flux through such pathways is dictated by the fractional stoichiometry of distinct modifications and protein assemblies as well as the spatial organ...

    journal_title:Molecular cell

    pub_type: 杂志文章,评审

    doi:10.1016/j.molcel.2015.02.020

    authors: Ordureau A,Münch C,Harper JW

    更新日期:2015-05-21 00:00:00

  • The APC/C subunit Mnd2/Apc15 promotes Cdc20 autoubiquitination and spindle assembly checkpoint inactivation.

    abstract::The fidelity of chromosome segregation depends on the spindle assembly checkpoint (SAC). In the presence of unattached kinetochores, anaphase is delayed when three SAC components (Mad2, Mad3/BubR1, and Bub3) inhibit Cdc20, the activating subunit of the anaphase-promoting complex (APC/C). We analyzed the role of Cdc20 ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2012.07.031

    authors: Foster SA,Morgan DO

    更新日期:2012-09-28 00:00:00

  • Multisite Phosphorylation of S6K1 Directs a Kinase Phospho-code that Determines Substrate Selection.

    abstract::Multisite phosphorylation of kinases can induce on-off or graded regulation of catalytic activity; however, its influence on substrate specificity remains unclear. Here, we show that multisite phosphorylation of ribosomal protein S6 kinase 1 (S6K1) alters target selection. Agonist-inducible phosphorylation of glutamyl...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2018.11.017

    authors: Arif A,Jia J,Willard B,Li X,Fox PL

    更新日期:2019-02-07 00:00:00

  • Mechanism of membrane insertion of a multimeric beta-barrel protein: perfringolysin O creates a pore using ordered and coupled conformational changes.

    abstract::Perfringolysin O, a bacterial cytolytic toxin, forms unusually large pores in cholesterol-containing membranes by the spontaneous insertion of two of its four domains into the bilayer. By monitoring the kinetics of domain-specific conformational changes and pore formation using fluorescence spectroscopy, the temporal ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(00)00119-2

    authors: Heuck AP,Hotze EM,Tweten RK,Johnson AE

    更新日期:2000-11-01 00:00:00

  • Nuclear RNA Exosome at 3.1 Å Reveals Substrate Specificities, RNA Paths, and Allosteric Inhibition of Rrp44/Dis3.

    abstract::The eukaryotic RNA exosome is an essential and conserved 3'-to-5' exoribonuclease complex that degrades or processes nearly every class of cellular RNA. The nuclear RNA exosome includes a 9-subunit non-catalytic core that binds Rrp44 (Dis3) and Rrp6 subunits to modulate their processive and distributive 3'-to-5' exori...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2016.09.038

    authors: Zinder JC,Wasmuth EV,Lima CD

    更新日期:2016-11-17 00:00:00

  • Tbf1 or not Tbf1?

    abstract::In this issue of Molecular Cell, Hogues et al. (2008) demonstrate a wholesale shift in the key regulatory protein involved in ribosomal protein (RP) synthesis during the evolution of S. cerevisiae and, en passant, raise interesting questions about the relationship between RP genes and telomeres. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2008.02.008

    authors: Bhattacharya A,Warner JR

    更新日期:2008-03-14 00:00:00

  • DNA Breaks and End Resection Measured Genome-wide by End Sequencing.

    abstract::DNA double-strand breaks (DSBs) arise during physiological transcription, DNA replication, and antigen receptor diversification. Mistargeting or misprocessing of DSBs can result in pathological structural variation and mutation. Here we describe a sensitive method (END-seq) to monitor DNA end resection and DSBs genome...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2016.06.034

    authors: Canela A,Sridharan S,Sciascia N,Tubbs A,Meltzer P,Sleckman BP,Nussenzweig A

    更新日期:2016-09-01 00:00:00

  • From Association to Causality: the Role of the Gut Microbiota and Its Functional Products on Host Metabolism.

    abstract::Many genomic studies have revealed associations between the gut microbiota composition and host metabolism. These observations led to the idea that a causal relationship could exist between the microbiota and metabolic diseases, a concept supported by studies showing compositional changes in the microbial community in...

    journal_title:Molecular cell

    pub_type: 杂志文章,评审

    doi:10.1016/j.molcel.2020.03.005

    authors: Koh A,Bäckhed F

    更新日期:2020-05-21 00:00:00

  • GPS2 is required for cholesterol efflux by triggering histone demethylation, LXR recruitment, and coregulator assembly at the ABCG1 locus.

    abstract::Transcriptional coregulators, rather than ligand signals, are suspected to confer context and pathway specificity to nuclear receptor signaling, but the identity of such specifying coregulators and the underlying molecular mechanisms remain largely enigmatic. Here we address this issue in metabolic oxysterol receptor ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2009.05.006

    authors: Jakobsson T,Venteclef N,Toresson G,Damdimopoulos AE,Ehrlund A,Lou X,Sanyal S,Steffensen KR,Gustafsson JA,Treuter E

    更新日期:2009-05-14 00:00:00

  • PoxA, yjeK, and elongation factor P coordinately modulate virulence and drug resistance in Salmonella enterica.

    abstract::We report an interaction between poxA, encoding a paralog of lysyl tRNA-synthetase, and the closely linked yjeK gene, encoding a putative 2,3-beta-lysine aminomutase, that is critical for virulence and stress resistance in Salmonella enterica. Salmonella poxA and yjeK mutants share extensive phenotypic pleiotropy, inc...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2010.06.021

    authors: Navarre WW,Zou SB,Roy H,Xie JL,Savchenko A,Singer A,Edvokimova E,Prost LR,Kumar R,Ibba M,Fang FC

    更新日期:2010-07-30 00:00:00

  • Histone chaperone spt16 promotes redeposition of the original h3-h4 histones evicted by elongating RNA polymerase.

    abstract::Nucleosomes are surprisingly dynamic structures in vivo, showing transcription-independent exchange of histones H2A-H2B genome-wide and exchange of H3-H4 mainly within the promoters of transcribed genes. In addition, nucleosomes are disrupted in front of and reassembled behind the elongating RNA polymerase. Here we sh...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2009.07.001

    authors: Jamai A,Puglisi A,Strubin M

    更新日期:2009-08-14 00:00:00

  • Cap-assisted internal initiation of translation of histone H4.

    abstract::In eukaryotes, a crucial step of translation initiation is the binding of the multifactor complex eIF4F to the 5' end of the mRNA, a prerequisite to recruitment of the activated small ribosomal 43S particle. Histone H4 mRNAs have short 5'UTRs, which do not conform to the conventional scanning-initiation model. Here we...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2010.12.019

    authors: Martin F,Barends S,Jaeger S,Schaeffer L,Prongidi-Fix L,Eriani G

    更新日期:2011-01-21 00:00:00

  • Involvement of transcription termination factor 2 in mitotic repression of transcription elongation.

    abstract::All nuclear transcription is interrupted during mitosis. We examined the role of human TTF2, an RNA polymerase (Pol) I and II termination factor, in mitotic repression of transcription elongation. We find that TTF2 levels rise in the cytoplasm in S and G2 and at the onset of mitosis TTF2 translocates into the nucleus....

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(04)00234-5

    authors: Jiang Y,Liu M,Spencer CA,Price DH

    更新日期:2004-05-07 00:00:00

  • Arginine/serine-rich domains of SR proteins can function as activators of pre-mRNA splicing.

    abstract::Serine/arginine (SR)-rich splicing factors contain an RNA binding domain and an arginine/serine (RS)-rich domain required for protein-protein interactions. In addition to their roles in the basic splicing reaction, SR proteins function as components of splicing enhancer complexes. Here, we investigate the role of RS d...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(00)80076-3

    authors: Graveley BR,Maniatis T

    更新日期:1998-04-01 00:00:00

  • Regulation of DNA-end resection by hnRNPU-like proteins promotes DNA double-strand break signaling and repair.

    abstract::DNA double-strand break (DSB) signaling and repair are critical for cell viability, and rely on highly coordinated pathways whose molecular organization is still incompletely understood. Here, we show that heterogeneous nuclear ribonucleoprotein U-like (hnRNPUL) proteins 1 and 2 play key roles in cellular responses to...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2011.12.035

    authors: Polo SE,Blackford AN,Chapman JR,Baskcomb L,Gravel S,Rusch A,Thomas A,Blundred R,Smith P,Kzhyshkowska J,Dobner T,Taylor AM,Turnell AS,Stewart GS,Grand RJ,Jackson SP

    更新日期:2012-02-24 00:00:00

  • RNA polymerase I contains a TFIIF-related DNA-binding subcomplex.

    abstract::The eukaryotic RNA polymerases Pol I, II, and III use different promoters to transcribe different classes of genes. Promoter usage relies on initiation factors, including TFIIF and TFIIE, in the case of Pol II. Here, we show that the Pol I-specific subunits A49 and A34.5 form a subcomplex that binds DNA and is related...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2010.07.028

    authors: Geiger SR,Lorenzen K,Schreieck A,Hanecker P,Kostrewa D,Heck AJ,Cramer P

    更新日期:2010-08-27 00:00:00

  • Features of ribosome-peptidyl-tRNA interactions essential for tryptophan induction of tna operon expression.

    abstract::Certain nascent peptide sequences, when within the ribosomal exit tunnel, can inhibit translation termination and/or peptide elongation. The 24 residue leader peptidyl-tRNA of the tna operon of E. coli, TnaC-tRNA(Pro), in the presence of excess tryptophan, resists cleavage at the tnaC stop codon. TnaC residue Trp12 is...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2005.06.013

    authors: Cruz-Vera LR,Rajagopal S,Squires C,Yanofsky C

    更新日期:2005-08-05 00:00:00

  • Robust Ordering of Anaphase Events by Adaptive Thresholds and Competing Degradation Pathways.

    abstract::The splitting of chromosomes in anaphase and their delivery into the daughter cells needs to be accurately executed to maintain genome stability. Chromosome splitting requires the degradation of securin, whereas the distribution of the chromosomes into the daughter cells requires the degradation of cyclin B. We show t...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2015.09.022

    authors: Kamenz J,Mihaljev T,Kubis A,Legewie S,Hauf S

    更新日期:2015-11-05 00:00:00

  • cIAPs block Ripoptosome formation, a RIP1/caspase-8 containing intracellular cell death complex differentially regulated by cFLIP isoforms.

    abstract::The intracellular regulation of cell death pathways by cIAPs has been enigmatic. Here we show that loss of cIAPs promotes the spontaneous formation of an intracellular platform that activates either apoptosis or necroptosis. This 2 MDa intracellular complex that we designate "Ripoptosome" is necessary but not sufficie...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2011.06.011

    authors: Feoktistova M,Geserick P,Kellert B,Dimitrova DP,Langlais C,Hupe M,Cain K,MacFarlane M,Häcker G,Leverkus M

    更新日期:2011-08-05 00:00:00

  • Stop codon recognition by release factors induces structural rearrangement of the ribosomal decoding center that is productive for peptide release.

    abstract::Peptide release on the ribosome is catalyzed in the large subunit peptidyl transferase center by release factors on recognition of stop codons in the small subunit decoding center. Here we examine the role of the decoding center in this process. Mutation of decoding center nucleotides or removal of 2'OH groups from th...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2007.09.015

    authors: Youngman EM,He SL,Nikstad LJ,Green R

    更新日期:2007-11-30 00:00:00

  • The pathway for DNA recognition and RNA integration by a group II intron retrotransposon.

    abstract::Group II intron RNPs are mobile genetic elements that attack and invade duplex DNA. In this work, we monitor the invasion reaction in vitro and establish a quantitative kinetic framework for the steps of this complex cascade. We find that target site specificity is achieved after DNA binding, which occurs nonspecifica...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(03)00069-8

    authors: Aizawa Y,Xiang Q,Lambowitz AM,Pyle AM

    更新日期:2003-03-01 00:00:00

  • The three-dimensional structure of the autoproteolytic, nuclear pore-targeting domain of the human nucleoporin Nup98.

    abstract::Nup98 is a component of the nuclear pore that plays its primary role in the export of RNAs. Nup98 is expressed in two forms, derived from alternate mRNA splicing. Both forms are processed into two peptides through autoproteolysis mediated by the C-terminal domain of hNup98. The three-dimensional structure of the C-ter...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(02)00589-0

    authors: Hodel AE,Hodel MR,Griffis ER,Hennig KA,Ratner GA,Xu S,Powers MA

    更新日期:2002-08-01 00:00:00