Post-Transcriptional Regulation of the Trypanosome Heat Shock Response by a Zinc Finger Protein

Dorothea Droll, Igor Minia, Abeer A. Fadda, Aditi Singh, Mhairi Stewart, Rafael Queiroz, Christine Clayton

Research output: Contribution to journalArticle

45 Citations (Scopus)

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.

Original languageEnglish
Article numbere1003286
JournalPLoS Pathogens
Volume9
Issue number4
DOIs
Publication statusPublished - Apr 2013
Externally publishedYes

Fingerprint

Heat-Shock Response
Trypanosomiasis
Zinc Fingers
Messenger RNA
Shock
HSP70 Heat-Shock Proteins
Hot Temperature
Proteins
Trypanosoma brucei brucei
Protein Refolding
3' Untranslated Regions
Heat-Shock Proteins
Genes
Insects
Parasites
RNA
Gene Expression
Temperature

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Post-Transcriptional Regulation of the Trypanosome Heat Shock Response by a Zinc Finger Protein. / Droll, Dorothea; Minia, Igor; Fadda, Abeer A.; Singh, Aditi; Stewart, Mhairi; Queiroz, Rafael; Clayton, Christine.

In: PLoS Pathogens, Vol. 9, No. 4, e1003286, 04.2013.

Research output: Contribution to journalArticle

Droll, Dorothea ; Minia, Igor ; Fadda, Abeer A. ; Singh, Aditi ; Stewart, Mhairi ; Queiroz, Rafael ; Clayton, Christine. / Post-Transcriptional Regulation of the Trypanosome Heat Shock Response by a Zinc Finger Protein. In: PLoS Pathogens. 2013 ; Vol. 9, No. 4.
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