Disease relevance of Tagetitoxin

• Tagetitoxin inhibits RNA synthesis directed by RNA polymerases from chloroplasts and Escherichia coli [1].
• Tagetitoxin, a chlorosis-inducing phytotoxin produced by Pseudomonas syringae pv. tagetis, inhibits RNA synthesis directed by chloroplast RNA polymerase [1].
• Tagetitoxin concentrations as high as 1 mM did not affect in vitro transcription reactions directed by RNA polymerase from bacteriophage T7 or SP6 [1].
• In HeLa cell extracts, accumulation of 5 S rRNA, and U6 snRNAs (transcribed by RNA polymerase III) was inhibited at 0.3-3.0 microM tagetitoxin but transcription from adenovirus 2 major late promoter (RNA polymerase II) was not significantly affected at concentrations below 30 microM [2].
• In vitro transcription from the 39K late promoter was resistant to high concentrations of both alpha-amanitin (100 micrograms/ml) and tagetitoxin (4,000 U/ml), suggesting that neither RNA polymerase II nor III is responsible for the transcription of baculovirus late genes [3].

High impact information on Tagetitoxin

• Transcription required supercoiled templates and was inhibited by tagetitoxin, an inhibitor of plastid transcription [4].
• Unlike other eukaryotic U2 snRNA genes, the T. brucei homolog is transcribed by an RNA polymerase III-like enzyme on the basis of its sensitivity to the inhibitors alpha-amanitin and tagetitoxin [5].
• In vitro transcription of TARE-6 was resistant to 1 microg/ml alpha-amanitin but sensitive to 100 microg/ml alpha-amanitin and tagetitoxin, suggesting involvement of RNA polymerase III [6].
• Tagetitoxin inhibition of in vitro transcription of the yeast SUP4 and SUP6 tRNA(Tyr) genes demonstrates template dependence and indicates that inhibition may occur after UMP incorporation [7].
• In addition, tagetitoxin inhibited in vitro RNA synthesis directed by the RNA polymerase from Escherichia coli [1].

Biological context of Tagetitoxin

• A mutant of Pseudomonas syringae pv. tagetis EB037 with limited ability to produce tagetitoxin was isolated after transposon mutagenesis and the mutation was characterized [8].

Anatomical context of Tagetitoxin

• In Xenopus oocytes, RNA polymerase III transcription was preferentially inhibited by tagetitoxin [2].
• In nonspecific transcription assays, partially purified B. mori RNA polymerase III was inhibited by tagetitoxin at concentrations that inhibit Escherichia coli RNA polymerase; purified calf thymus RNA polymerase II was not inhibited by tagetitoxin [2].

Associations of Tagetitoxin with other chemical compounds

• A synthesis of the 9-oxa-3-thiabicyclo[3.3.1]nonane ring system, which constitutes the core of the RNA polymerase inhibitor tagetitoxin, has been achieved through cyclisation of a thiol onto an electrophilic ketone [9].

Gene context of Tagetitoxin

• However, our in vitro transcription study reveals that transcription from the human L1 promoter is highly sensitive to tagetitoxin, a selective inhibitor of RNA polymerase III (pol III), but insensitive to 1 micrograms/ml of alpha-amanitin, indicating that the human L1 promoter is pol III-dependent [10].
• The effect of tagetitoxin is selective because this compound does not inhibit barley leaf growth, or the normal accumulation of nuclear-encoded actin and BN3 transcripts and plastid DNA which occurs during chloroplast development [11].

Analytical, diagnostic and therapeutic context of Tagetitoxin

• The turnover of RNAs encoded by seven different barley chloroplast genes was analyzed after treatment of barley shoots with tagetitoxin, a selective inhibitor of chloroplast transcription [12].

References