Post-transcriptional regulation of the trypanosome heat shock response by a zinc finger protein.
Post-transcriptional regulation of the trypanosome heat shock response by a zinc finger protein.
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DOI：
10.1371/journal.ppat.1003286
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发表时间：
2013
期刊：
影响因子：
6.7
通讯作者：
Clayton C
中科院分区：
文献类型：
--
作者：
Droll D;Minia I;Fadda A;Singh A;Stewart M;Queiroz R;Clayton C
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. When organisms are placed at a temperature that is higher than normal, their proteins start to unfold. The organisms protect themselves by increasing the synthesis of “heat-shock” proteins which can re-fold other proteins when the temperature returns to normal. In trypanosomes, the degradation of mRNAs that encode heat-shock proteins is slowed down at elevated temperatures. Trypanosoma brucei multiplies as “bloodstream forms” in the blood of mammals, at temperatures between 37–39°C; and as “procyclic forms” in Tsetse flies, which are usually at 20–37°C but can survive at 41°C. In this paper we show that in Trypanosoma brucei, a protein called ZC3H11 can bind to many heat-shock-protein mRNAs. ZC3H11 is essential in bloodstream-form trypanosomes and for recovery of procyclic-form trypanosomes after heat shock. ZC3H11 binds to an AUU repeat motif which is found in parts of the target mRNAs that do not encode protein. Several heat-shock-protein RNAs were decreased when we decreased the amount of ZC3H11 in bloodstream-form trypanosomes. These and other results show that expression of the specific subset of trypanosome heat-shock proteins is controlled by the interaction of ZC3H11 with the relevant mRNAs. They also show that the heat-shock response could enhance survival of trypanosomes in over-heated Tsetse flies.
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DOI：
10.1093/bioinformatics/btr064
发表时间：
2011-04-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Grant CE;Bailey TL;Noble WS
通讯作者：
Noble WS
影响因子：
5.3
作者：
Clement, Sandra L.;Scheckel, Claudia;Lykke-Andersen, Jens
通讯作者：
Lykke-Andersen, Jens
影响因子：
1.5
作者：
Brems, S;Guilbride, DL;Clayton, C
通讯作者：
Clayton, C
影响因子：
4.5
作者：
David, Maya;Gabdank, Idan;Shapira, Michal
通讯作者：
Shapira, Michal
影响因子：
1.5
作者：
Alsford, S;Glover, L;Horn, D
通讯作者：
Horn, D