title: Post-transcriptional regulation of the trypanosome heat shock response by a zinc finger protein.
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.
authors.affiliation: Zentrum für Molekulare Biologie der Universität Heidelberg-ZMBH, DKFZ-ZMBH Alliance, Heidelberg, Germany.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Droll
authors.forename: Igor
authors.initials: I
authors.lastname: Minia
authors.forename: Abeer
authors.initials: A
authors.lastname: Fadda
authors.forename: Aditi
authors.initials: A
authors.lastname: Singh
authors.forename: Mhairi
authors.initials: M
authors.lastname: Stewart
authors.forename: Rafael
authors.initials: R
authors.lastname: Queiroz
authors.forename: Christine
authors.initials: C
authors.lastname: Clayton
mesh_terms: D002460:Cell Line; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018869:Heat-Shock Response / Q000235:genetics*; D006801:Humans; D011485:Protein Binding; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012323:RNA Processing, Post-Transcriptional; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016053:RNA, Protozoan / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D014346:Trypanosoma brucei brucei / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers / Q000235:genetics
chemical_list: D018840:HSP70 Heat-Shock Proteins; D015800:Protozoan Proteins; D012333:RNA, Messenger; D016053:RNA, Protozoan; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins