amanitins

Summary

Summary: Cyclic peptides extracted from carpophores of various mushroom species. They are potent inhibitors of RNA polymerases in most eukaryotic species, blocking the production of mRNA and protein synthesis. These peptides are important in the study of transcription. Alpha-amanitin is the main toxin from the species Amanitia phalloides, poisonous if ingested by humans or animals.

Top Publications

  1. Letschert K, Faulstich H, Keller D, Keppler D. Molecular characterization and inhibition of amanitin uptake into human hepatocytes. Toxicol Sci. 2006;91:140-9 pubmed
    ..In conclusion, we have identified OATP1B3 as the human hepatic uptake transporter for amatoxins; moreover, substrates and inhibitors of OATP1B3, among others rifampicin, may be useful for the treatment of human amatoxin poisoning. ..
  2. Gong X, Nedialkov Y, Burton Z. Alpha-amanitin blocks translocation by human RNA polymerase II. J Biol Chem. 2004;279:27422-7 pubmed
    ..Because initially resistant elongation complexes form only a single phosphodiester bond before being rendered inactive in the following bond addition cycle, alpha-amanitin inhibits elongation at each translocation step. ..
  3. Bushnell D, Cramer P, Kornberg R. Structural basis of transcription: alpha-amanitin-RNA polymerase II cocrystal at 2.8 A resolution. Proc Natl Acad Sci U S A. 2002;99:1218-22 pubmed
    ..The structure of the complex indicates the likely basis of inhibition and gives unexpected insight into the transcription mechanism. ..
  4. Archambault J, Friesen J. Genetics of eukaryotic RNA polymerases I, II, and III. Microbiol Rev. 1993;57:703-24 pubmed
  5. Listerman I, Bledau A, Grishina I, Neugebauer K. Extragenic accumulation of RNA polymerase II enhances transcription by RNA polymerase III. PLoS Genet. 2007;3:e212 pubmed
    ..Consequently, Pol II coordinates expression of all RNA and protein components of the spliceosome. ..
  6. Misteli T, Spector D. RNA polymerase II targets pre-mRNA splicing factors to transcription sites in vivo. Mol Cell. 1999;3:697-705 pubmed
    ..Our results demonstrate a critical role for the CTD of RNA pol II LS in the intranuclear targeting of splicing factors to transcription sites in vivo. ..
  7. Thiriet C, Hayes J. Replication-independent core histone dynamics at transcriptionally active loci in vivo. Genes Dev. 2005;19:677-82 pubmed
  8. Chafin D, Guo H, Price D. Action of alpha-amanitin during pyrophosphorolysis and elongation by RNA polymerase II. J Biol Chem. 1995;270:19114-9 pubmed
    ..Since polymerase molecules encounter similar kinetic barriers during both processes, it is possible that there is a common step in the reverse movement of the polymerase. ..
  9. Edgar B, Datar S. Zygotic degradation of two maternal Cdc25 mRNAs terminates Drosophila's early cell cycle program. Genes Dev. 1996;10:1966-77 pubmed
    ..Unlike timing or counting mechanisms, this mechanism can compensate for losses or additions of nuclei by altering the timing and number of the maternal cycles and thus will always generate the correct cell density at the MZT. ..

More Information

Publications62

  1. Myers F, Francis Lang H, Newbury S. Degradation of maternal string mRNA is controlled by proteins encoded on maternally contributed transcripts. Mech Dev. 1995;51:217-26 pubmed
    ..Therefore, the proteins required to activate the degradation of string mRNA are encoded on a maternally contributed mRNA. We discuss possible models to explain the degradation pathway. ..
  2. Kunkel G, Maser R, Calvet J, Pederson T. U6 small nuclear RNA is transcribed by RNA polymerase III. Proc Natl Acad Sci U S A. 1986;83:8575-9 pubmed
    ..These results establish that, in contrast to the polymerase II-directed transcription of mammalian genes for U1-U5 small nuclear RNAs, human U6 RNA is transcribed by RNA polymerase III. ..
  3. Raha D, Wang Z, Moqtaderi Z, Wu L, Zhong G, Gerstein M, et al. Close association of RNA polymerase II and many transcription factors with Pol III genes. Proc Natl Acad Sci U S A. 2010;107:3639-44 pubmed publisher
    ..These results indicate that, contrary to previous expectations, polymerases can often work with one another to globally coordinate gene expression. ..
  4. Kramer P, Fragoso G, Pennie W, Htun H, Hager G, Sinden R. Transcriptional state of the mouse mammary tumor virus promoter can affect topological domain size in vivo. J Biol Chem. 1999;274:28590-7 pubmed
    ..These results suggest that topological domain boundaries can be "functional" in nature, being established by the formation of activated and elongating transcription complexes. ..
  5. Arima Y, Nitta M, Kuninaka S, Zhang D, Fujiwara T, Taya Y, et al. Transcriptional blockade induces p53-dependent apoptosis associated with translocation of p53 to mitochondria. J Biol Chem. 2005;280:19166-76 pubmed
    ..Our data thus suggested that blockade of pol II-mediated transcription induced p53 accumulation in mitochondria and was the critical factor for eliciting p53-dependent but transcription-independent apoptosis. ..
  6. Spann T, Goldman A, Wang C, Huang S, Goldman R. Alteration of nuclear lamin organization inhibits RNA polymerase II-dependent transcription. J Cell Biol. 2002;156:603-8 pubmed
    ..Furthermore, immunofluorescence observations indicate that this selective inhibition of polymerase II-dependent transcription involves the TATA binding protein, a component of the basal transcription factor TFIID. ..
  7. Enjalbert F, Rapior S, Nouguier Soulé J, Guillon S, Amouroux N, Cabot C. Treatment of amatoxin poisoning: 20-year retrospective analysis. J Toxicol Clin Toxicol. 2002;40:715-57 pubmed
    ..The major amatoxins, the alpha-, beta-, and gamma-amanitins, are bicyclic octapeptide derivatives that damage the liver and kidney via irreversible binding to RNA ..
  8. Kim K, Choi S, Park K, Seok S, Lee K. Cytotoxic constituents of Amanita subjunquillea. Arch Pharm Res. 2008;31:579-86 pubmed publisher
    ..Compound 9 exhibited significant cytotoxic activity against A549, SK-OV-3, SK-MEL-2 and HCT15 with ED(50) values of 1.47, 0.26, 1.57 and 1.32 microM, respectively. ..
  9. Aggarwal B, Calvi B. Chromatin regulates origin activity in Drosophila follicle cells. Nature. 2004;430:372-6 pubmed
    ..These results suggest that nucleosome acetylation and other epigenetic changes are important modulators of origin activity in metazoa. ..
  10. Klink V, Wolniak S. Centrin is necessary for the formation of the motile apparatus in spermatids of Marsilea. Mol Biol Cell. 2001;12:761-76 pubmed
    ..These results show that centrin plays an essential role in the formation of a motile apparatus during spermiogenesis of M. vestita. ..
  11. Zinszner H, Immanuel D, Yin Y, Liang F, Ron D. A topogenic role for the oncogenic N-terminus of TLS: nucleolar localization when transcription is inhibited. Oncogene. 1997;14:451-61 pubmed
  12. Wen X, Lei Y, Zhou Y, Okamoto C, Snead M, Paine M. Structural organization and cellular localization of tuftelin-interacting protein 11 (TFIP11). Cell Mol Life Sci. 2005;62:1038-46 pubmed
    ..The TFIP body may therefore represent a new subnuclear storage compartment for splicing components...
  13. Wills B, Haller N, Peter D, White L. Use of amifostine, a novel cytoprotective, in alpha-amanitin poisoning. Clin Toxicol (Phila). 2005;43:261-7 pubmed
    ..0002). No survival benefit was seen with cumulative doses between 250 and 500 mg/kg; however, higher doses may result in subsequent toxicity and decreased survival. ..
  14. Umehara M, Totsuka E, Ishizawa Y, Nara M, Hakamada K, Umehara Y, et al. A bioartificial liver that combines plasma dialysis and whole liver perfusion. Hepatogastroenterology. 2008;55:1216-21 pubmed
    ..Extracorporeal liver, perfused with oxygenated plasma, functioned for 6 h without hyperacute rejection. This type of hybrid bioartificial liver may be useful for treating FHF patients. ..
  15. Vanacova S, Tachezy J, Ullu E, Tschudi C. Unusual diversity in alpha-amanitin sensitivity of RNA polymerases in trichomonads. Mol Biochem Parasitol. 2001;115:239-47 pubmed
  16. Svetlova M, Solovjeva L, Pleskach N, Yartseva N, Yakovleva T, Tomilin N, et al. Clustered sites of DNA repair synthesis during early nucleotide excision repair in ultraviolet light-irradiated quiescent human fibroblasts. Exp Cell Res. 2002;276:284-95 pubmed
    ..The residual foci detected in CS cells indicate that, even at early times following UV irradiation, GGR may open some chromatin domains for processive scanning and consequent DRS independent of transcription. ..
  17. Vianna M, Igaz L, Coitinho A, Medina J, Izquierdo I. Memory extinction requires gene expression in rat hippocampus. Neurobiol Learn Mem. 2003;79:199-203 pubmed
    ..These requirements are to be expected from learning that involves new synaptic associations. ..
  18. De Carlo E, Milanesi A, Martini C, Maffei P, Tamagno G, Parnigotto P, et al. Effects of Amanita phalloides toxins on insulin release: in vivo and in vitro studies. Arch Toxicol. 2003;77:441-5 pubmed
    ..These observations show that Amanita toxins might play a role in the clinical context of Amanita poisoning. We demonstrate, for the first time, that alpha-amanitin induces insulin release and may exert a cytotoxic effect on beta cells. ..
  19. da Silva W, Bonini J, Bevilaqua L, Medina J, Izquierdo I, Cammarota M. Inhibition of mRNA synthesis in the hippocampus impairs consolidation and reconsolidation of spatial memory. Hippocampus. 2008;18:29-39 pubmed
  20. Bonnet M, Basson P. The toxicology of Amanita virosa: the destroying angel. Homeopathy. 2004;93:216-20 pubmed
    ..Symptoms of human poisoning by A. virosa are described, following the order of Homeopathic Repertories. Laboratory values for comparison with normal values of haematology, biochemistry and urine analyses are given...
  21. Chang J, Nie X, Gudima S, Taylor J. Action of inhibitors on accumulation of processed hepatitis delta virus RNAs. J Virol. 2006;80:3205-14 pubmed
  22. Evangelisti C, Riccio M, Faenza I, Zini N, Hozumi Y, Goto K, et al. Subnuclear localization and differentiation-dependent increased expression of DGK-zeta in C2C12 mouse myoblasts. J Cell Physiol. 2006;209:370-8 pubmed
    ..Overall, our findings further support the importance of speckles and nuclear matrix in lipid-dependent signaling and suggest that nuclear DGK-zeta might play some fundamental role during myogenic differentiation of C2C12 cells. ..
  23. Arkhipova I. Complex patterns of transcription of a Drosophila retrotransposon in vivo and in vitro by RNA polymerases II and III. Nucleic Acids Res. 1995;23:4480-7 pubmed
    ..A possible role of pol III transcription in mechanisms controlling the expression of full-length mdg1-encoded transcripts in the developing fly, which are apparently relaxed in cell culture, is discussed. ..
  24. Aeby E, Ullu E, Yepiskoposyan H, Schimanski B, Roditi I, Mühlemann O, et al. tRNASec is transcribed by RNA polymerase II in Trypanosoma brucei but not in humans. Nucleic Acids Res. 2010;38:5833-43 pubmed publisher
    ..Moreover, intron-encoded tRNAs are present in a number of eukaryotic genomes indicating that Pol-II transcription of tRNAs may not be restricted to trypanosomatids. ..
  25. Medcalf R, Ruegg M, Schleuning W. A DNA motif related to the cAMP-responsive element and an exon-located activator protein-2 binding site in the human tissue-type plasminogen activator gene promoter cooperate in basal expression and convey activation by phorbol ester and cAMP. J Biol Chem. 1990;265:14618-26 pubmed
    ..The results of band-shift analysis and competition titration experiments demonstrate that the CRE-like element acts as a low affinity binding site for the same proteins which recognize the authentic CRE. ..
  26. Jan M, Siddiqui T, Ahmed N, Ul Haq I, Khan Z. Mushroom poisoning in children: clinical presentation and outcome. J Ayub Med Coll Abbottabad. 2008;20:99-101 pubmed
    ..To start timely management, Mushroom poisoning should be considered in the differential diagnosis in patients presenting with food poisoning particularly coming in groups. Delay in diagnosis is associated with high mortality. ..
  27. Zhang P, Chen Z, Hu J, Wei B, Zhang Z, Hu W. Production and characterization of Amanitin toxins from a pure culture of Amanita exitialis. FEMS Microbiol Lett. 2005;252:223-8 pubmed
    ..3 +/- 43.8 microg g(-1) (dry matter) of alpha-Amanitin and 60.0 +/- 20.7 microg g(-1) (dry matter) of beta-Amanitin, respectively, a yield which is about 10% of that produced by fruiting bodies. ..
  28. Serra M, Carrillo C, González N, Algranati I. Modulation of oat arginine decarboxylase gene expression and genome organization in transgenic Trypanosoma cruzi epimastigotes. FEBS J. 2006;273:628-37 pubmed
    ..4 Mbp) bearing a ribosomal RNA locus. The sensitivity of transcription to alpha-amanitin strongly suggests involvement of the protozoan RNA polymerase I in the transcription of the exogenous ADC gene. ..
  29. Giannini L, Vannacci A, Missanelli A, Mastroianni R, Mannaioni P, Moroni F, et al. Amatoxin poisoning: a 15-year retrospective analysis and follow-up evaluation of 105 patients. Clin Toxicol (Phila). 2007;45:539-42 pubmed
    ..Fatalities due to mushroom poisonings are increasing worldwide, with more than 90% of deaths resulting from ingestion of amatoxin-containing species...
  30. Wang I, Chang H, Shen C. Actin-based modeling of a transcriptionally competent nuclear substructure induced by transcription inhibition. Exp Cell Res. 2006;312:3796-807 pubmed
  31. Rogalski T, Golomb M, Riddle D. Mutant Caenorhabditis elegans RNA polymerase II with a 20,000-fold reduced sensitivity to alpha-amanitin. Genetics. 1990;126:889-98 pubmed
    ..The highly resistant double mutant was selected among four million progeny of the mutagenized ama-1(m118) parent by its ability to grow and reproduce in 200 micrograms/ml amanitin in the presence of a permeabilizing agent, Triton X-100. ..
  32. Fabian D, Bukovská A, Juhás S, Koppel J. Apoptotic processes and DNA cytosine methylation in mouse embryos arrested at the 2-cell stage. Zygote. 2009;17:269-79 pubmed publisher
    ..Although observed apoptotic cells showed either demethylated or methylated DNA cytosine in their nuclei, at blastocyst stage the demethylated status appeared more frequently in them. ..
  33. Lim J, Bustin M, Ogryzko V, Postnikov Y. Metastable macromolecular complexes containing high mobility group nucleosome-binding chromosomal proteins in HeLa nuclei. J Biol Chem. 2002;277:20774-82 pubmed
    ..We suggest that the inclusion of HMGN proteins into metastable multiprotein complexes serves to target the HMGN proteins to specific sites in chromatin and enhances their interaction with nucleosomes. ..
  34. Loreni F, Thomas G, Amaldi F. Transcription inhibitors stimulate translation of 5' TOP mRNAs through activation of S6 kinase and the mTOR/FRAP signalling pathway. Eur J Biochem. 2000;267:6594-601 pubmed
    ..These results indicate that the effect of act D on translation is mediated by the S6Ks through FRAP/mTOR. ..
  35. Frenkel G, Ducote J, Reboulleau C, Gierthy J. A cell line with decreased sensitivity to the methyl mercury-induced stimulation of alpha-amanitin sensitive RNA synthesis in isolated nuclei. Comp Biochem Physiol B. 1988;91:477-82 pubmed
    ..5. The B50 and HeLa cells were also compared as to their sensitivity to other effects of methyl mercury. ..
  36. Sordet O, Redon C, Guirouilh Barbat J, Smith S, Solier S, Douarre C, et al. Ataxia telangiectasia mutated activation by transcription- and topoisomerase I-induced DNA double-strand breaks. EMBO Rep. 2009;10:887-93 pubmed publisher
    ..Thus, we propose that Top1cc produce transcription arrests with R-loop formation and generate DSBs that activate ATM in post-mitotic cells. ..
  37. Xu X, Zhang J, Cai Z, Zhang J, Huang B, Xu J, et al. [Determination of amanitins and phallotoxins in wild mushrooms by online liquid chromatography-diode array detector-tandem mass spectrometry]. Se Pu. 2017;35:613-619 pubmed publisher
    A fast and wide linear range method was established for the determination of mushroom toxins amanitins (α-amanitin,β-amanitin and γ-amanitin) and phallotoxins (phallacidin and phalloidin) in wild mushrooms by ..
  38. Forró M, Mándli T. [Liver transplantation after Amanita phalloides poisoning from the viewpoint of anesthesia and intensive care based on three cases]. Orv Hetil. 2003;144:269-73 pubmed
    ..Pancreatitis, DIC, gastrointestinal bleeding, acute renal failure were found at all patients, therefore liver transplantation is only a part of the treatment, complex therapy is necessary in this cases. ..
  39. Berger K, Guss D. Mycotoxins revisited: Part I. J Emerg Med. 2005;28:53-62 pubmed
    ..Part II, to be published in the next issue of the Journal, will be focused on the presentation of the other classes of toxic mushrooms along with an up-to-date review of the most recently identified poisonous varieties. ..
  40. Gaunitz F, Heise K, Schumann R, Gebhardt R. Glucocorticoid induced expression of glutamine synthetase in hepatoma cells. Biochem Biophys Res Commun. 2002;296:1026-32 pubmed
    ..However, evidence is presented that aside from a primary effect on transcription glucocorticoids mediate their effect on the expression of GS also at the posttranscriptional level. ..
  41. Chun R, Jeang K. Requirements for RNA polymerase II carboxyl-terminal domain for activated transcription of human retroviruses human T-cell lymphotropic virus I and HIV-1. J Biol Chem. 1996;271:27888-94 pubmed
    ..Taken together, these observations address mechanistic corollaries between activators with(out) a linked CTD kinase and regulated transcription by RNA polymerase II moieties with(out) a CTD. ..
  42. Bjerregaard B, Wrenzycki C, Strejcek F, Laurincik J, Holm P, Ochs R, et al. Expression of nucleolar-related proteins in porcine preimplantation embryos produced in vivo and in vitro. Biol Reprod. 2004;70:867-76 pubmed
    ..These findings show, to our knowledge for the first time, a nucleolus-related gene expression in the preimplantation porcine embryo, and they highlight the differences in quality between in vivo and in vitro-produced embryos. ..
  43. Xu Z, Tsuji T, Riordan J, Hu G. The nuclear function of angiogenin in endothelial cells is related to rRNA production. Biochem Biophys Res Commun. 2002;294:287-92 pubmed
  44. Arima Y, Hirota T, Bronner C, Mousli M, Fujiwara T, Niwa S, et al. Down-regulation of nuclear protein ICBP90 by p53/p21Cip1/WAF1-dependent DNA-damage checkpoint signals contributes to cell cycle arrest at G1/S transition. Genes Cells. 2004;9:131-42 pubmed
    ..Deregulation of ICBP90 may impair the control of G1/S transition during checkpoint activation and lead to genomic instability. ..
  45. Singhal P, DeCandido S, Satriano J, Schlondorff D, Hays R. Atrial natriuretic peptide and nitroprusside cause relaxation of cultured rat mesangial cells. Am J Physiol. 1989;257:C86-93 pubmed
    ..ANP (10(-10)-10(-8) M) as well as NP (10(-5) M) increased intracellular cGMP content of MC (P less than 0.005) compared with control cells.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  46. Riede I. Tumor therapy with Amanita phalloides (death cap): stabilization of B-cell chronic lymphatic leukemia. J Altern Complement Med. 2010;16:1129-32 pubmed publisher
    ..No leukemia-associated symptoms, liver damage, or continuous erythrocyte deprivation occur. This new principle of tumor therapy shows high potential to provide a gentle medical treatment. ..
  47. Robinson Fuentes V, Jaime Sánchez J, García Aguilar L, Gómez Peralta M, Vázquez Garcidueñas M, Vázquez Marrufo G. Determination of alpha- and beta-amanitin in clinical urine samples by Capillary Zone Electrophoresis. J Pharm Biomed Anal. 2008;47:913-7 pubmed publisher
    b>Amanitins are toxins found in species of the mushroom genera Amanita, Lepiota and Galerina. Intoxication after ingestion of these mushrooms can be fatal with an estimated 20% of mortality rate...
  48. Park J, Werner J, Kim J, Lis J, Kim Y. Mediator, not holoenzyme, is directly recruited to the heat shock promoter by HSF upon heat shock. Mol Cell. 2001;8:9-19 pubmed
    ..Therefore, the activator-Mediator interaction likely underlies the initiation of signal transfer from enhancer-bound activators to the basal transcription machinery. ..
  49. Das A, Li H, Liu T, Bellofatto V. Biochemical characterization of Trypanosoma brucei RNA polymerase II. Mol Biochem Parasitol. 2006;150:201-10 pubmed
    ..brucei RNA polymerase II. While both bioinformatics and biochemical analysis have focused on the subunit structure of trypanosome RNA polymerases, this is the first study that reveals a functional RNA polymerase II enzyme. ..
  50. Swiech L, Kisiel K, Czolowska R, Zientarski M, Borsuk E. Accumulation and dynamics of proteins of the MCM family during mouse oogenesis and the first embryonic cell cycle. Int J Dev Biol. 2007;51:283-95 pubmed
    ..In the one-cell embryo, insoluble Mcm2 appeared in the G1 nucleus, persisted in the S phase and was undetectable in the G2 nucleus. Such behavior of Mcm2 supports its involvement in chromatin licensing in the first embryonic cell cycle. ..
  51. Sekine K, Hase T, Sato N. Reversible DNA compaction by sulfite reductase regulates transcriptional activity of chloroplast nucleoids. J Biol Chem. 2002;277:24399-404 pubmed
    ..These results suggest that SiR regulates the transcriptional activity of chloroplast nucleoids through changes in DNA compaction. ..
  52. Igaz L, Vianna M, Medina J, Izquierdo I. Two time periods of hippocampal mRNA synthesis are required for memory consolidation of fear-motivated learning. J Neurosci. 2002;22:6781-9 pubmed
  53. Hamet P, Malo D, Tremblay J. Increased transcription of a major stress gene in spontaneously hypertensive mice. Hypertension. 1990;15:904-8 pubmed
    ..The genetic basis of environmental susceptibility to hypertension may thus involve an abnormal control of heat shock genes. ..