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.
Highlights
When living organisms are exposed to temperatures above their growth optima, they respond by increased synthesis of heat-shock proteins
Trypanosoma brucei and related Kinetoplastid protists must adapt to different temperatures: they multiply both in mammals, with temperatures varying from 32uC to 38uC depending on species and body location, and in arthropod vectors in which the temperature variations are much greater (e.g. [8])
When organisms are placed at a temperature that is higher than normal, their proteins start to unfold
Summary
When living organisms are exposed to temperatures above their growth optima, they respond by increased synthesis of heat-shock proteins. [5,6,7]), and in arthropod vectors in which the temperature variations are much greater In Kinetoplastids, the regulation relies exclusively on post-transcriptional mechanisms. Transcription is polycistronic [9,10], and individual mRNAs are produced by trans splicing and polyadenylation [11,12]. The final cytoplasmic RNA level is determined by the rates of processing, transport from the nucleus, and degradation [13]. For most trypanosome mRNAs, the rate of degradation is a critical determinant of expression [14]
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