Discussion

Transitions towards trypanosomes differentiation are complex and require well coordinated gene expression programs. Unlike other eukaryotes, transcription in trypanosome is polycistronic; many basal transcription factors are missing. In absence of RNA polymerase II dependent transcription regulation, what are the regulatory factors that triggers changes in trypanosome gene expression and ensures irreversibility after the initial differentiation signal? We here show that a single T. brucei RNA binding protein-RBP10 acts as an on/off switch which defines the trypanosome differentiation state. RBP10 is a cytosolic RNA-binding protein which is expressed only in multiplying bloodstream forms. The bloodstream forms depleted of RBP10 can survive only as procyclic forms. More remarkably, expression of RBP10 in procyclic forms results in their direct conversion to bloodstream forms within 2 days. RBP10 binds to procyclic-specific mRNAs containing the sequence UAUUUUUU, targeting them for translation repression and destruction. The products of RBP10 target mRNAs include not only the major procyclic-specific surface protein and various enzymes of energy metabolism, but also signaling and RNA-binding proteins required for procyclic-form survival. RBP10 is therefore a paradigm for the definition and maintenance of a eukaryotic cell differentiation state by a post-transcriptional regulatory cascade.