We have analysed the effect of transcription inhibitors on the polysomal localization of 5' terminal oligopyrimidine (TOP-) mRNAs. It is known that, in vertebrates, the translation of this group of mRNAs is regulated according to the growth status of the cell. Mitogenic stimulation of quiescent cells induces a rapid recruitment of TOP mRNAs from translationally inactive light messenger ribonucleoprotein particles to polysomes. It was found that administration of transcription inhibitors to resting cells causes a similar collective translational activation of TOP mRNAs, without affecting global translation. A number of transcription inhibitors were tested in amphibian and mammalian cultured cells. Actinomycin D (act D), cordycepin, and 5,6-dichloro-1-beta -d-ribofuranosylbenzimidazole caused a similar activation whereas alpha -amanitin or low doses of act D did not induce the translational response. Concentrations of act D sufficient to induce TOP mRNA translation also induce 40S ribosomal protein S6 kinases 1 (S6K1) activation. Moreover at these concentrations of act D increased phosphorylation of 4E-BP1 was also observed, indicating the involvement of FRAP/mTOR. Consistent with this observation, pretreatment of resting cells with rapamycin suppresses the activation of TOP mRNA translation induced by act D. These results indicate that the effect of act D on translation is mediated by the S6Ks through FRAP/mTOR.

Loreni, F., Thomas, G., & Amaldi, F. (2000). Transcription inhibitors stimulate translation of 5 ' TOP mRNAs through activation of S6 kinase and the mTOR/FRAP signalling pathway. EUROPEAN JOURNAL OF BIOCHEMISTRY, 267(22), 6594-6601 [10.1046/j.1432-1327.2000.01753.x].

Transcription inhibitors stimulate translation of 5 ' TOP mRNAs through activation of S6 kinase and the mTOR/FRAP signalling pathway

LORENI, FABRIZIO;AMALDI, FRANCESCO
2000

Abstract

We have analysed the effect of transcription inhibitors on the polysomal localization of 5' terminal oligopyrimidine (TOP-) mRNAs. It is known that, in vertebrates, the translation of this group of mRNAs is regulated according to the growth status of the cell. Mitogenic stimulation of quiescent cells induces a rapid recruitment of TOP mRNAs from translationally inactive light messenger ribonucleoprotein particles to polysomes. It was found that administration of transcription inhibitors to resting cells causes a similar collective translational activation of TOP mRNAs, without affecting global translation. A number of transcription inhibitors were tested in amphibian and mammalian cultured cells. Actinomycin D (act D), cordycepin, and 5,6-dichloro-1-beta -d-ribofuranosylbenzimidazole caused a similar activation whereas alpha -amanitin or low doses of act D did not induce the translational response. Concentrations of act D sufficient to induce TOP mRNA translation also induce 40S ribosomal protein S6 kinases 1 (S6K1) activation. Moreover at these concentrations of act D increased phosphorylation of 4E-BP1 was also observed, indicating the involvement of FRAP/mTOR. Consistent with this observation, pretreatment of resting cells with rapamycin suppresses the activation of TOP mRNA translation induced by act D. These results indicate that the effect of act D on translation is mediated by the S6Ks through FRAP/mTOR.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/11
English
Con Impact Factor ISI
5,6 dichlorobenzimidazole riboside; alpha amanitin; cordycepin; dactinomycin; messenger RNA; pyrimidine derivative; rapamycin; ribosome protein; S6 kinase; 5' untranslated region; animal cell; article; cell stimulation; controlled study; enzyme activation; gene activation; gene repression; human; human cell; mitogenesis; nonhuman; priority journal; protein phosphorylation; regulatory mechanism; RNA translation; signal transduction; Amanitins; Animals; Cell Cycle Proteins; Cells, Cultured; Dactinomycin; Deoxyadenosines; Dichlororibofuranosylbenzimidazole; Enzyme Activation; Kidney; Nucleic Acid Synthesis Inhibitors; Phosphotransferases (Alcohol Group Acceptor); Protein Biosynthesis; Protein Kinases; Protein-Serine-Threonine Kinases; Ribosomal Protein S6 Kinases; RNA, Messenger; Signal Transduction; Transcription, Genetic; Vertebrates; Xenopus laevis; Xenopus Proteins; Amphibia; Animalia; Mammalia; Vertebrata
Loreni, F., Thomas, G., & Amaldi, F. (2000). Transcription inhibitors stimulate translation of 5 ' TOP mRNAs through activation of S6 kinase and the mTOR/FRAP signalling pathway. EUROPEAN JOURNAL OF BIOCHEMISTRY, 267(22), 6594-6601 [10.1046/j.1432-1327.2000.01753.x].
Loreni, F; Thomas, G; Amaldi, F
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/48120
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