Post-transcriptional regulation of the trypanosome heat shock response by a zinc finger protein

• Verfasst von: Droll, Dorothea [VerfasserIn]
• Verfasst von: Minia, Igor [VerfasserIn]
• Verfasst von: Fadda, Abeer [VerfasserIn]
• Verfasst von: Singh, Aditi [VerfasserIn]
• Verfasst von: Stewart, Mhairi [VerfasserIn]
• Verfasst von: Queiroz, Rafael [VerfasserIn]
• Verfasst von: Clayton, Christine [VerfasserIn]
• Titel: Post-transcriptional regulation of the trypanosome heat shock response by a zinc finger protein
• Verf.angabe: Dorothea Droll, Igor Minia, Abeer Fadda, Aditi Singh, Mhairi Stewart, Rafael Queiroz, Christine Clayton
• E-Jahr: 2013
• Jahr: April 4, 2013
• Fussnoten: Gesehen am 05.01.2021
• Titel Quelle: Enthalten in: Public Library of SciencePLoS pathogens
• Ort Quelle: Lawrence, Kan. : PLoS, 2005
• Jahr Quelle: 2013
• Band/Heft Quelle: 9(2013,4) Artikel-Nummer e1003286, 17 Seiten
• ISSN Quelle: 1553-7374
• DOI: doi:10.1371/journal.ppat.1003286
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Heat shock response
• Sach-SW: Messenger RNA
• Sach-SW: Northern blot
• Sach-SW: RNA interference
• Sach-SW: RNA-binding proteins
• Sach-SW: Trypanosoma
• Sach-SW: Trypanosoma brucei
• Sach-SW: Zinc finger domains
• K10plus-PPN: 1743906196

Abstract

In most organisms, the heat-shock response involves increased heat-shock gene transcription. In Kinetoplastid protists, however, virtually all control of gene expression is post-transcriptional. Correspondingly, Trypanosoma brucei heat-shock protein 70 (HSP70) synthesis after heat shock depends on regulation of HSP70 mRNA turnover. We here show that the T. brucei CCCH zinc finger protein ZC3H11 is a post-transcriptional regulator of trypanosome chaperone mRNAs. ZC3H11 is essential in bloodstream-form trypanosomes and for recovery of insect-form trypanosomes from heat shock. ZC3H11 binds to mRNAs encoding heat-shock protein homologues, with clear specificity for the subset of trypanosome chaperones that is required for protein refolding. In procyclic forms, ZC3H11 was required for stabilisation of target chaperone-encoding mRNAs after heat shock, and the HSP70 mRNA was also decreased upon ZC3H11 depletion in bloodstream forms. Many mRNAs bound to ZC3H11 have a consensus AUU repeat motif in the 3′-untranslated region. ZC3H11 bound preferentially to AUU repeats in vitro, and ZC3H11 regulation of HSP70 mRNA in bloodstream forms depended on its AUU repeat region. Tethering of ZC3H11 to a reporter mRNA increased reporter expression, showing that it is capable of actively stabilizing an mRNA. These results show that expression of trypanosome heat-shock genes is controlled by a specific RNA-protein interaction. They also show that heat-shock-induced chaperone expression in procyclic trypanosome enhances parasite survival at elevated temperatures.