We have compared the transcriptomes of cultured procyclicTrypanosoma bruceicells in early and late logarithmic phases and found that ∼200 mRNAs were differentially regulated. In late log phase cells, the most upregulated mRNA encoded the nucleobase transporter NT8. The 3′ untranslated region (UTR) ofNT8contains a short stem–loopcis-element that is necessary for the regulation ofNT8expression in response to external purine levels. When placed in the 3′-UTR of an unregulated transcript, thecis-element is sufficient to confer regulation in response to purines. To our knowledge, this is the first example of a discrete RNA element that can autonomously regulate gene expression in trypanosomes in response to an external factor and reveals an unprecedented purine-dependent signaling pathway that controls gene expression in eukaryotes.