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Volume 3, 2012 - Issue 6
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Point of View

Elongator

Transcriptional or translational regulator?

Sebastian Glatt European Molecular Biology Laboratory; Structural and Computational Biology Unit; Heidelberg, Germany
,
Bertrand Séraphin Equipe Labellisée La Ligue; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC); Institut National de Santé et de Recherche Médicale (INSERM) U964/Centre National de Recherche Scientifique (CNRS) UMR 7104/Université de Strasbourg; Illkirch, France; Centre de Génétique Moléculaire; CNRS UPR 3404; Gif sur Yvette, France
&
Christoph W. Müller European Molecular Biology Laboratory; Structural and Computational Biology Unit; Heidelberg, GermanyCorrespondencecmueller@embl.de
Pages 273-276
Published online: 14 Aug 2012

Point of View

Elongator

Transcriptional or translational regulator?

Abstract

The conserved multi-subunit Elongator complex was initially described as a RNA polymerase II (RNAPII) associated transcription elongation factor, but since has been shown to be involved a variety of different cellular activities. Here, we summarize recent developments in the field and discuss the resulting implications for the proposed multi-functionality of Elongator.

Introduction

Elongator is a large macromolecular complex (~900 kDa) that is built up by two copies of each of its six subunits (named Elongator proteins Elp1–6).1 The importance of each of the individual subunits for Elongator function is not only highlighted by the high degree of sequence conservation from yeast to human, but also by the fact that the deletion of any of the subunits leads to the loss of Elongator complex integrity, its dysfunction and almost identical phenotypes in Saccharomyces cerevisiae, Caenorhabditis elegans, Arabidopsis thaliana and Drosophila melanogaster.2-7 Since its discovery, the cellular functions of Elongator are controversially discussed,8,9 as it has been implicated in different cellular activities, including protein acetylation,10-12 exocytosis,13 sensitivity to DNA damaging agents,14 zygotic paternal DNA demethylation15 and tRNA modification16 (summarized in Figure 1).

Figure 1. Elongator complex assembly and its proposed cellular functions. The upper panel shows a schematic representation of the Elongator subcomplex arrangement. The central hexameric Elp456 subcomplex is shown in cartoon representation (Elp4 in green; Elp5 in blue; Elp6 in brown) and is flanked by two copies of the Elp123 subcomplex. Predicted domains in Elp123 are marked individually (WD40 domains, tetratricopeptide repeats (TPR); histone acetyl transferase (HAT); radical S-adenosyl-methionine (rSAM); iron-sulfur cluster - FeS). The lower panel highlights tRNA modification (translational control) and histone acetylation (transcriptional control) as Elongator’s proposed cellular functions. Additional functions, which were shown to be indirectly affected by Elongator role in tRNA modifications are DNA damage response,44 telomeric gene silencing,44 exocytosis,16 cell cycle regulation,35 transcriptional activation16 and chromatin remodeling.16 Functions that could indirectly result from translational/transcriptional activities of Elongator or because the proteins involved are additional direct targets of Elongator such as α-tubulin/Bruchpilot acetylation12 or paternal genome demethylation15 are listed separately.

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In humans, several studies could show that patients suffering from certain neurodegenerative diseases carry mutations or variants in one of the six human Elongator genes.17-19 A complete mechanistic understanding of specific roles of Elongator in nerve cells is still missing, but it has been suggested that nerve cells are particular sensitive to translational defects because of their markedly higher rates of protein synthesis compared with other cell types.5,12,20 Contradictory reports present Elongator as a dual regulator of transcription and translation complicating the quest for a unique targeted treatment strategy for the benefit of the patients. Clarifying whether Elongator regulates a multitude of cellular activities through a global transcriptional or translational mechanism therefore has become a high priority.

Elongator - A Transcriptional Regulator?

The presence of a conserved Histone Acetyl Transferase (HAT) domain in Elp311 and co-purification of Elongator with RNAP II21 initially led to the conclusion that Elongator might facilitate transcription elongation by acetylating histone tails, a post-transcriptional chromatin mark generally associated with actively transcribed genes.22 Surprisingly, a genome wide study on transcription elongation factors could not find any association or enrichment of Elongator at actively transcribed genomic regions.23 Later, Elongator was believed to interact with nascent mRNA during transcription elongation,24 but in a recent study, designed to identify the complete human interactome of chromatin-associated messenger ribonucleoproteins by proteomics, no Elongator subunits could be detected, either.25 Furthermore, the sub-cellular localization of Elongator subunits seems to be mainly cytoplasmic. This localization apparently contradicts its assigned role in transcriptional elongation, although it was shown that some subunits in certain organisms could localize to the nucleus.10,12,26-29 Although Elp3 was indeed reported to acetylate histones in vitro,11,27 it was recently implicated in the acetylation of Bruchpilot, an integral component of the presynaptic density at the periphery of neuronal cells.10 This modification could directly link Elongator-dependent protein acetylation to the reported neuronal phenotypes of patients with Elongator mutations.

In summary, although the observation that Elongator is involved in a whole variety of cellular activities could indeed be explained by its ability to impact on the transcription of a set of genes that are involved in those cellular activities, there is accumulating evidence in the literature that the initial concepts suggesting a direct involvement of Elongator in transcription elongation by RNAP II have to be confirmed and challenged by future in vivo and in vitro studies.

Elongator – A Translation Regulator?

Elongator was shown to directly interact with eukaryotic tRNAs in vitro1,3 (but not with single stranded DNA or RNA) and is required for the formation of 5-methoxycarbonylmethyl (mcm5) and 5-carbamoylmethyl (ncm5) groups on uridine nucleosides present at the wobble position of many tRNAs.3,30 During a screen for yeast factors conferring resistance to the Kluyveromyces lactis γ-toxin (zymocin), all six Elongator genes were identified together with other factors known to affect the tRNA modification of the same tRNA residue.30 Consistent with the observation that Elongator mutant strains are resistant to zymocin, it was shown that mcm5 modified uridines in tRNAs represent the specific target sites for the toxin.2,31 Strikingly, Esberg and colleagues16 have shown that most cellular phenotypes, including those originally associated with the role of Elongator in transcription elongation, could be rescued by overexpressing two yeast tRNAs whose modifications are Elongator-dependent. This thereby provided the first body of evidence that the function of Elongator in tRNA modification might result in a wide variety of phenotypes through its global impact on translation (Fig. 1).

The biochemical details of the contribution of Elongator (together with other factors) to tRNA modification are still unresolved, although it was recently shown that so-called radical S-Adenosyl Methionione (SAM) domains, of which one is present in the N-terminus of Elp3,32 are able to mediate the transfer of methyl groups to RNAs.33 Strikingly, mutations affecting the conserved active site residues in the HAT domain of Elp3, formerly exclusively associated with histone acetylation, result in the loss of tRNA modification activity of Elongator.3 The formation of the rather complicated ncm5/mcm5 modification, which occurs, for a few tRNAs, on the same wobble uridine in the wobble base position that is also thiolated, enhances translation efficiency and accuracy.34 A very recent report by Bauer and colleagues clearly supports that Elongator is indeed affecting the translation of a whole variety of cellular proteins.35 Strikingly, these translational alterations are tightly correlated with the codon usage of the affected genes, namely the bias toward codons, that are translated by Elongator-dependent modified tRNAs.

In summary, the surprising finding that certain tRNA species can rescue phenotypes originally associated with Elongator direct role in several cellular activities, might be simply explained by its tRNA modification activity and the subsequent changes in the translation of a whole variety of target mRNAs.

Structural Dissection of Elongator and the Consequences for its Substrate Recognition

Recently, the first structural information of a part of the Elongator complex at atomic resolution was obtained, namely the crystal structure of the Elp456 subcomplex.1,36 The crystal structure, in combination with additional structural, biochemical, biophysical and in vivo analyses, revealed the hetero-hexameric nature of the Elp456 subcomplex (Elp456). Unexpectedly, Elp4, Elp5 and Elp6 all share the same RecA like protein fold and are arranged in a ring-like fashion, known from homo-hexameric members of the RecA-like NTPase family.37 The hetero-hexameric assembly provides a logical explanation to the earlier observation that single deletions of the three Elp456 subunits lead to identical in vivo phenotypes. In addition, it was shown that the hexameric conformation of Elp456 is essential for its ability to bind to the anti-codon stem-loops (ACLs) of tRNAs.1 tRNA binding was shown to be abolished in mutants targeting the central cavity of the ring, particularly the homologous nucleic acid binding loops (L2) of Elp6, known from RecA, Rho, and other members of the hexameric NTPases to bind specifically to nucleic acids. Similar as other RecA-like NTPases, Elp456 is able to hydrolyze ATP and to use this hydrolysis reaction to regulate its association to tRNAs.1 In this scenario, ATP recruitment and hydrolysis in the Elp456 ATPase sites, localized on the outside of the inter-subunit interfaces, would induce conformational changes in the distant tRNA binding loops, localized in the central cavity, allowing the release of a tRNA molecule. After ATP hydrolysis, the hydrolyzed nucleotides would be released, which would allow Elp456 to bind to the next tRNA molecule and induce its modification. How the temporal control of this regulatory circuit is orchestrated is not fully understood yet, but intensive research efforts are currently ongoing.

The conservation throughout evolution of a hetero-hexameric ring might be simply explained by preserving substrate specificity toward tRNA stem loops or other particles harboring pseudo 2-fold symmetry. In addition, a hetero-hexameric assembly facilitates the specific positioning of only two copies of the associated Elp123 subcomplexes on a hexameric central Elp456 particle. It was shown that the above described structure-function analysis of the separated Elp456 hexamer can be translated into the fully assembled Elongator complex, as Elp4, Elp5 and Elp6 are incorporated into the full complex as a hexameric assembly.

Discussion and Conclusions

Obviously, the most intriguing questions concern the substrate specificity and enzymatic activity of the Elongator complex. Although data on its involvement in tRNA modification are recently accumulating,1,3,16,35 further supporting a role of Elongator in this activity, the existence of additional substrates and molecular activities more related to its role in transcription regulation cannot be fully excluded yet. Some Elongator functions might also only be found in certain organisms and thereby underline the active evolutionary process that has affected this macromolecular complex. The possibility remains that alternative assemblies of Elongator subunits exist in the cell that catalyze different molecular activities. Indeed, if it was reported that Elongator dissociates into two subcomplexes at higher salt concentration,38 it remains possible, for example, that individual subunits might interact with different associated factors.29,39-43 The latter would, however, be inconsistent with the similar phenotypes observed upon inactivation of different Elp subunits. Detailed co-localization studies of all six Elongator proteins in different organisms should help clarify if alternative compositions exist, are specific to certain organisms, and are localized in different sub-cellular compartments.

Structural analyses of subunits Elp1, Elp2, Elp3 and the fully assembled Elongator complex will allow a better molecular understanding of this large complex in the future. On one hand, low and medium resolution analyses of the fully assembled Elongator will help understand inter-subunit communication and the influence of associated factors and substrate recognition for the overall architecture of Elongator. On the other hand, high resolution structural information will allow a detailed description of the chemical reactions catalyzed by Elongator during tRNA modification, interaction with partners involved in this process and, potentially, other modifying activities of the Elongator complex. Further investigations of the tRNA recognition mechanism by Elongator might also lead to a structural explanation of how the anti-codon loop is recognized and why only uridines in the wobble position of the tRNA are subject to this specific modification reaction, whereas uridines in other positions remain unmodified. In summary, novel structural insights will continue to complement known and ongoing functional studies on Elongator and will contribute to understand the true nature of this highly conserved cellular machine.

References

  • Glatt S, Létoquart J, Faux C, Taylor NM, Séraphin B, Müller CW. The Elongator subcomplex Elp456 is a hexameric RecA-like ATPase. Nat Struct Mol Biol 2012; 19:314 - 20; http://dx.doi.org/10.1038/nsmb.2234; PMID: 22343726  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Frohloff F, Fichtner L, Jablonowski D, Breunig KD, Schaffrath R. Saccharomyces cerevisiae Elongator mutations confer resistance to the Kluyveromyces lactis zymocin. EMBO J 2001; 20:1993 - 2003; http://dx.doi.org/10.1093/emboj/20.8.1993; PMID: 11296232  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Huang B, Johansson MJO, Byström AS. An early step in wobble uridine tRNA modification requires the Elongator complex. RNA 2005; 11:424 - 36; http://dx.doi.org/10.1261/rna.7247705; PMID: 15769872  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Mehlgarten C, Jablonowski D, Wrackmeyer U, Tschitschmann S, Sondermann D, Jäger G, et al. Elongator function in tRNA wobble uridine modification is conserved between yeast and plants. Mol Microbiol 2010; 76:1082 - 94; http://dx.doi.org/10.1111/j.1365-2958.2010.07163.x; PMID: 20398216  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Chen CC, Tuck S, Byström AS. Defects in tRNA modification associated with neurological and developmental dysfunctions in Caenorhabditis elegans elongator mutants. PLoS Genet 2009; 5:e1000561; http://dx.doi.org/10.1371/journal.pgen.1000561; PMID: 19593383  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Walker J, Kwon SY, Badenhorst P, East P, McNeill H, Svejstrup JQ. Role of elongator subunit Elp3 in Drosophila melanogaster larval development and immunity. Genetics 2011; 187:1067 - 75; http://dx.doi.org/10.1534/genetics.110.123893; PMID: 21288872  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Singh N, Lorbeck MT, Zervos A, Zimmerman J, Elefant F. The histone acetyltransferase Elp3 plays in active role in the control of synaptic bouton expansion and sleep in Drosophila. J Neurochem 2010; 115:493 - 504; http://dx.doi.org/10.1111/j.1471-4159.2010.06892.x; PMID: 20626565  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Versées W, De Groeve S, Van Lijsebettens M. Elongator, a conserved multitasking complex?. Mol Microbiol 2010; 76:1065 - 9; http://dx.doi.org/10.1111/j.1365-2958.2010.07162.x; PMID: 20398217  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Svejstrup JQ. Elongator complex: how many roles does it play?. Curr Opin Cell Biol 2007; 19:331 - 6; http://dx.doi.org/10.1016/j.ceb.2007.04.005; PMID: 17466506  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Miśkiewicz K, Jose LE, Bento-Abreu A, Fislage M, Taes I, Kasprowicz J, et al. ELP3 controls active zone morphology by acetylating the ELKS family member Bruchpilot. Neuron 2011; 72:776 - 88; http://dx.doi.org/10.1016/j.neuron.2011.10.010; PMID: 22153374  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Wittschieben BO, Otero G, de Bizemont T, Fellows J, Erdjument-Bromage H, Ohba R, et al. A novel histone acetyltransferase is an integral subunit of elongating RNA polymerase II holoenzyme. Mol Cell 1999; 4:123 - 8; http://dx.doi.org/10.1016/S1097-2765(00)80194-X; PMID: 10445034  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Creppe C, Malinouskaya L, Volvert ML, Gillard M, Close P, Malaise O, et al. Elongator controls the migration and differentiation of cortical neurons through acetylation of alpha-tubulin. Cell 2009; 136:551 - 64; http://dx.doi.org/10.1016/j.cell.2008.11.043; PMID: 19185337  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Rahl PB, Chen CZ, Collins RN. Elp1p, the yeast homolog of the FD disease syndrome protein, negatively regulates exocytosis independently of transcriptional elongation. Mol Cell 2005; 17:841 - 53; http://dx.doi.org/10.1016/j.molcel.2005.02.018; PMID: 15780940  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Li Q, Fazly AM, Zhou H, Huang SB, Zhang ZG, Stillman B. The elongator complex interacts with PCNA and modulates transcriptional silencing and sensitivity to DNA damage agents. PLoS Genet 2009; 5:e1000684; http://dx.doi.org/10.1371/journal.pgen.1000684; PMID: 19834596  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Okada Y, Yamagata K, Hong K, Wakayama T, Zhang Y. A role for the elongator complex in zygotic paternal genome demethylation. Nature 2010; 463:554 - 8; http://dx.doi.org/10.1038/nature08732; PMID: 20054296  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Esberg A, Huang B, Johansson MJO, Byström AS. Elevated levels of two tRNA species bypass the requirement for elongator complex in transcription and exocytosis. Mol Cell 2006; 24:139 - 48; http://dx.doi.org/10.1016/j.molcel.2006.07.031; PMID: 17018299  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Anderson SL, Coli R, Daly IW, Kichula EA, Rork MJ, Volpi SA, et al. Familial dysautonomia is caused by mutations of the IKAP gene. Am J Hum Genet 2001; 68:753 - 8; http://dx.doi.org/10.1086/318808; PMID: 11179021  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Simpson CL, Lemmens R, Miskiewicz K, Broom WJ, Hansen VK, van Vught PWJ, et al. Variants of the elongator protein 3 (ELP3) gene are associated with motor neuron degeneration. Hum Mol Genet 2009; 18:472 - 81; http://dx.doi.org/10.1093/hmg/ddn375; PMID: 18996918  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Strug LJ, Clarke T, Chiang T, Chien MC, Baskurt Z, Li WL, et al. Centrotemporal sharp wave EEG trait in rolandic epilepsy maps to Elongator Protein Complex 4 (ELP4). Eur J Hum Genet 2009; 17:1171 - 81; http://dx.doi.org/10.1038/ejhg.2008.267; PMID: 19172991  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Lemmens R, Moore MJ, Al-Chalabi A, Brown RH Jr., Robberecht W. RNA metabolism and the pathogenesis of motor neuron diseases. Trends Neurosci 2010; 33:249 - 58; http://dx.doi.org/10.1016/j.tins.2010.02.003; PMID: 20227117  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Otero G, Fellows J, Li Y, de Bizemont T, Dirac AMG, Gustafsson CM, et al. Elongator, a multisubunit component of a novel RNA polymerase II holoenzyme for transcriptional elongation. Mol Cell 1999; 3:109 - 18; http://dx.doi.org/10.1016/S1097-2765(00)80179-3; PMID: 10024884  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Pokholok DK, Harbison CT, Levine S, Cole M, Hannett NM, Lee TI, et al. Genome-wide map of nucleosome acetylation and methylation in yeast. Cell 2005; 122:517 - 27; http://dx.doi.org/10.1016/j.cell.2005.06.026; PMID: 16122420  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Pokholok DK, Hannett NM, Young RA. Exchange of RNA polymerase II initiation and elongation factors during gene expression in vivo. Mol Cell 2002; 9:799 - 809; http://dx.doi.org/10.1016/S1097-2765(02)00502-6; PMID: 11983171  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Gilbert C, Kristjuhan A, Winkler GS, Svejstrup JQ. Elongator interactions with nascent mRNA revealed by RNA immunoprecipitation. Mol Cell 2004; 14:457 - 64; http://dx.doi.org/10.1016/S1097-2765(04)00239-4; PMID: 15149595  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Close P, East P, Dirac-Svejstrup AB, Hartmann H, Heron M, Maslen S, et al. DBIRD complex integrates alternative mRNA splicing with RNA polymerase II transcript elongation. Nature 2012; 484:386 - 9; http://dx.doi.org/10.1038/nature10925; PMID: 22446626  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Hawkes NA, Otero G, Winkler GS, Marshall N, Dahmus ME, Krappmann D, et al. Purification and characterization of the human elongator complex. J Biol Chem 2002; 277:3047 - 52; http://dx.doi.org/10.1074/jbc.M110445200; PMID: 11714725  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Kim JH, Lane WS, Reinberg D. Human Elongator facilitates RNA polymerase II transcription through chromatin. Proc Natl Acad Sci U S A 2002; 99:1241 - 6; PMID: 11818576  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Solinger JA, Paolinelli R, Klöss H, Scorza FB, Marchesi S, Sauder U, et al. The Caenorhabditis elegans Elongator complex regulates neuronal alpha-tubulin acetylation. PLoS Genet 2010; 6:e1000820; http://dx.doi.org/10.1371/journal.pgen.1000820; PMID: 20107598  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Fichtner L, Frohloff F, Jablonowski D, Stark MJ, Schaffrath R. Protein interactions within Saccharomyces cerevisiae Elongator, a complex essential for Kluyveromyces lactis zymocicity. Mol Microbiol 2002; 45:817 - 26; http://dx.doi.org/10.1046/j.1365-2958.2002.03055.x; PMID: 12139626  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Huang B, Lu J, Byström AS. A genome-wide screen identifies genes required for formation of the wobble nucleoside 5-methoxycarbonylmethyl-2-thiouridine in Saccharomyces cerevisiae. RNA 2008; 14:2183 - 94; http://dx.doi.org/10.1261/rna.1184108; PMID: 18755837  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Lu J, Huang B, Esberg A, Johansson MJ, Byström AS. The Kluyveromyces lactis gamma-toxin targets tRNA anticodons. RNA 2005; 11:1648 - 54; http://dx.doi.org/10.1261/rna.2172105; PMID: 16244131  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Paraskevopoulou C, Fairhurst SA, Lowe DJ, Brick P, Onesti S. The Elongator subunit Elp3 contains a Fe4S4 cluster and binds S-adenosylmethionine. Mol Microbiol 2006; 59:795 - 806; http://dx.doi.org/10.1111/j.1365-2958.2005.04989.x; PMID: 16420352  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Boal AK, Grove TL, McLaughlin MI, Yennawar NH, Booker SJ, Rosenzweig AC. Structural basis for methyl transfer by a radical SAM enzyme. Science 2011; 332:1089 - 92; http://dx.doi.org/10.1126/science.1205358; PMID: 21527678  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Vendeix FA, Murphy FV 4th, Cantara WA, Leszczyńska G, Gustilo EM, Sproat B, et al. Human tRNA(Lys3)(UUU) is pre-structured by natural modifications for cognate and wobble codon binding through keto-enol tautomerism. J Mol Biol 2012; 416:467 - 85; http://dx.doi.org/10.1016/j.jmb.2011.12.048; PMID: 22227389  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Bauer. Translational Control of Cell Division by Elongator. Cell Reports 2012; 1:424 - 33; http://dx.doi.org/10.1016/j.celrep.2012.04.001; PMID: 22768388  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Lin Z, Zhao W, Diao W, Xie X, Wang Z, Zhang J, et al. Crystal structure of elongator subcomplex elp4-6. J Biol Chem 2012; 287:21501 - 8; http://dx.doi.org/10.1074/jbc.M112.341560; PMID: 22556426  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Lyubimov AY, Strycharska M, Berger JM. The nuts and bolts of ring-translocase structure and mechanism. Curr Opin Struct Biol 2011; 21:240 - 8; http://dx.doi.org/10.1016/j.sbi.2011.01.002; PMID: 21282052  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Winkler GS, Petrakis TG, Ethelberg S, Tokunaga M, Erdjument-Bromage H, Tempst P, et al. RNA polymerase II elongator holoenzyme is composed of two discrete subcomplexes. J Biol Chem 2001; 276:32743 - 9; http://dx.doi.org/10.1074/jbc.M105303200; PMID: 11435442  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Cohen L, Henzel WJ, Baeuerle PA. IKAP is a scaffold protein of the IkappaB kinase complex. Nature 1998; 395:292 - 6; http://dx.doi.org/10.1038/26254; PMID: 9751059  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Collum RG, Brutsaert S, Lee G, Schindler CA. A Stat3-interacting protein (StIP1) regulates cytokine signal transduction. Proc Natl Acad Sci U S A 2000; 97:10120 - 5; http://dx.doi.org/10.1073/pnas.170192197; PMID: 10954736  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Fichtner L, Frohloff F, Bürkner K, Larsen M, Breunig KD, Schaffrath R. Molecular analysis of KTI12/TOT4, a Saccharomyces cerevisiae gene required for Kluyveromyces lactis zymocin action. Mol Microbiol 2002; 43:783 - 91; http://dx.doi.org/10.1046/j.1365-2958.2002.02794.x; PMID: 11929532  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Frohloff F, Jablonowski D, Fichtner L, Schaffrath R. Subunit communications crucial for the functional integrity of the yeast RNA polymerase II elongator (gamma-toxin target (TOT)) complex. J Biol Chem 2003; 278:956 - 61; http://dx.doi.org/10.1074/jbc.M210060200; PMID: 12424236  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Mehlgarten C, Jablonowski D, Breunig KD, Stark MJ, Schaffrath R. Elongator function depends on antagonistic regulation by casein kinase Hrr25 and protein phosphatase Sit4. Mol Microbiol 2009; 73:869 - 81; http://dx.doi.org/10.1111/j.1365-2958.2009.06811.x; PMID: 19656297  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
  • Chen C, Huang B, Eliasson M, Rydén P, Byström AS. Elongator complex influences telomeric gene silencing and DNA damage response by its role in wobble uridine tRNA modification. PLoS Genet 2011; 7:e1002258; http://dx.doi.org/10.1371/journal.pgen.1002258; PMID: 21912530  [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
 

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