Discussion

Trypanosoma brucei, the causative agent of Human African Trypanosomiasis (HAT) commutes between two markedly different environments, the human host and the tsetse fly. In the blood and tissue fluids of mammals it experiences temperatures ranging from 36°C to 40°C . In the tsetse fly glands or gut, the trypanosomes may experience temperature fluctuations depending on the environment the fly is exposed to (25°C-42°C). In such hostile conditions the parasite experiences stress which it must overcome in order to survive. Trypanosomes like other kinetoplastids overcome such stress by post-transcriptional gene regulation. Transcription in these kinetoplastids are polycistronic; premature mRNAs are spliced to generate mature mRNA that undergo translation. Therefore, the regulation of gene expression almost exclusively relies on the trans-acting factors like RNA Binding Proteins (RBPs). The fate of a mRNA depends on the function of the partner RBP. Some RBPs bind to certain recognition motifs located on the 3’UTR, or sometimes within the open reading frame (ORF) of the target mRNA. If the RBP interacts with protein binding partners like PBP1, PABP1, or MKT1, it is likely to stabilise the mRNA for translation, and lower the chances of its degradation. On the other hand, RBPs which interact with deadenylases like CAF1, CCR4, ribonucleases,and with the exosome machinary, will lead to the destabilisation and dragradation of its target mRNA. The RBP ZC3H30 can bind to reporter gene constructs and decrease the expression by destabilising the transcript. The expression of ZC3H30 in not necessary for the survival of the pathogen under normal growth condition. But, when the cells are inflicted with stress (heat shock, arsenite and ethanol), the cells that lack the expression do not survive. It will be interesting to find the constituents of the transcriptome and proteome of the ZC3H30knockouts, which might illuminate the cause of its hypersensitivity to stress.