Regulating a Post-Transcriptional Regulator: Protein Phosphorylation, Degradation and Translational Blockage in Control of the Trypanosome Stress-Response RNA-Binding Protein ZC3H11

摘要: The life cycle of the mammalian pathogen Trypanosoma brucei involves commuting between two markedly different environments: homeothermic host and poikilothermic invertebrate vector. ability to resist temperature other stresses is essential for trypanosome survival. Trypanosome gene expression mainly post-transcriptional, but must nevertheless be adjusted in response environmental cues, including host-specific physical chemical stresses. We investigate here control ZC3H11, a CCCH zinc finger protein which stabilizes stress mRNAs. ZC3H11 levels increase at least 10-fold when trypanosomes are stressed by heat shock, proteasome inhibitors, ethanol, arsenite, low doses puromycin, not various found that increases stability translation efficiency both contribute accumulation. an vitro substrate casein kinase 1 isoform 2 (CK1.2), results from CK1.2 depletion experiments suggest phosphorylation can promote its instability vivo. Results sucrose density centrifugation indicate under normal culture conditions initiation on mRNA repressed, after suitable moves heavy polysomes. 3'-UTR sufficient suppression region 71 nucleotides required regulation. Since works bloodstream forms, where repressed 37°C, procyclic activated we predict this regulatory RNA sequence targeted repressive trans acting factor released upon stress.