Discussion

Trypanosoma brucei obtains the essential element iron by uptake of host transferrin through its own transferrin receptor. Under iron starvation conditions, expression of the transferrin receptor rapidly increases equally at the mRNA and protein level, suggesting that regulation occurs through an unknown post-transcriptional mechanism (Fast et al., 1999). The T. brucei transferrin receptor is a heterodimer of the glycoproteins ESAG6 and ESAG7, with the former containing a GPI anchor to facilitate attachment to the plasma membrane. We identified the ESAG6 3’UTR by reverse transcription of mRNA, and to study its function we fused the 3’UTR onto reporter genes encoding GFP or firefly Luciferase (fLUC) and inserted them into the 2T1 bloodstream form cell line at the tagged RRNA locus. Iron starvation conditions, induced by addition of iron chelators or by switching from bovine to canine serum, resulted in rapid upregulation of the reporter proteins consistent with the magnitude and timing of the previously reported upregulation of the transferrin receptor. We conclude that i. the dynamic regulation of the T. brucei transferrin receptor is mediated via its 3’UTR, and ii. the effect is independent of the ES body, Pol I transcription and proximity to the telomere.

References: Fast et al, 1999, Biochem.