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

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. © 2013 droll et al.