PT  - JOURNAL ARTICLE
AU  - Corinna Benz
AU  - Winston Lo
AU  - Nadin Fathallah
AU  - Ashley Connor-Guscott
AU  - Henry J. Benns
AU  - Michael D Urbaniak
TI  - Dynamic regulation of the <em>Trypanosoma brucei</em> transferrin receptor in response to iron starvation is mediated <em>via</em> the 3’UTR
AID  - 10.1101/441931
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 441931
4099  - http://biorxiv.org/content/early/2018/10/12/441931.short
4100  - http://biorxiv.org/content/early/2018/10/12/441931.full
AB  - The bloodstream form of the parasite Trypanosoma brucei obtains iron from its mammalian host by receptor-mediated endocytosis of host transferrin through its own unique transferrin receptor (TbTfR). Expression of TbTfR rapidly increases upon iron starvation by post-transcriptional regulation through a currently undefined mechanism that is distinct from the mammalian iron response system. We have created reporter cell lines by fusing the TbTfR 3′UTR or a control Aldolase 3’UTR to reporter genes encoding GFP or firefly Luciferase, and inserted the fusions into a bloodstream form cell line at a tagged ribosomal RNA locus. Fusion of the TbTfR 3’UTR is sufficient to significantly repress the expression of the reporter proteins under normal growth conditions. Under iron starvation conditions we observed upregulation of the TbTfR 3’UTR fusions only, with a magnitude and timing consistent with that reported for upregulation of the TbTfR. We conclude that the dynamic regulation of the T. brucei transferrin receptor in response to iron starvation is mediated via its 3’UTR, and that the effect is independent of genomic location.