TcUBP-1, a Developmentally Regulated U-rich RNA-binding Protein Involved in Selective MRNA Destabilization in Trypanosomes

Developmental stages of the trypanosome life cycle differ in their morphology, biology, and biochemical properties. Consequently, several proteins have to be tightly regulated in their expression to allow trypanosomes to adapt rapidly to sudden environmental changes, a process that might be of central importance for parasite survival. However, in contrast to higher eukaryotic cells, trypanosomes do not seem to regulate gene expression through regulation of transcription initiation. These parasites make use of post-transcriptional regulatory mechanisms and modification of mRNA half-life is a relevant one. Trans-acting factors binding to cis-elements that affect mRNA stability of mature transcripts have not been identified in these cells. In this work, a novel U-rich RNA-binding protein (TcUBP-1) from Trypanosoma cruzi, the agent of Chagas disease, was identified. Its structure includes an RNA recognition motif, a nuclear export signal, and auxiliary domains with glycine- and glutamine-rich regions. TcUBP-1 recognizes the 44-nucleotide AU-rich RNA instability element located in the 3'-untranslated region of mucin SMUG mRNAs (Di Noia, J. M., D'Orso, I., Sanchez, D. O., and Frasch, A. C. (2000) J. Biol. Chem. 275, 10218-10227) as well as GU-rich sequences. Over-expression of TcUBP-1 in trypanosomes decreases the half-life of SMUG mucin mRNAs in vivo but does not affect the stability of other parasite mRNAs. Because TcUBP-1 is developmentally regulated, it might have a relevant role in regulating protein expression during trypanosome differentiation, allowing a correct expression pattern of U-rich-containing mRNAs.