During its life cycle, Trypanosoma brucei multiplies in the blood of infected individuals as the bloodstream form and in the midgut of Tsetse flies as the procyclic form. Changes in mRNA and protein levels accompany these developmental transitions. Mugo and Clayton now show that the RNA-binding protein RBP10 promotes the development of the bloodstream form of T. brucei and functions as an on–off regulatory switch. The authors showed that the depletion of RBP10 from bloodstream forms promoted their conversion into procyclic forms, whereas its expression had the opposite effect. In addition, they found that RBP10 bound to procyclic-specific mRNAs that contained an UAUUUUUU motif in the 3′ UTR and targeted them for translational repression and degradation. Target mRNAs included a major procyclic surface protein, metabolic enzymes, kinases and stage-specific RNA-binding proteins, which suggests that RBP10 may control a post-transcriptional regulatory cascade.