RNA editing in trypanosomes occurs by a series of enzymatic steps that are catalyzed by a macromolecular complex. The TbMP52 protein is shown to be a component of this complex, to have RNA ligase activity, and to be one of two adenylatable proteins in the complex. Regulated repression of TbMP52 blocks editing, which shows that it is a functional component of the editing complex. This repression is lethal in bloodforms of the parasite, indicating that editing is essential in the mammalian stage of the life cycle. The editing complex, which is present in all kinetoplastid parasites, may thus be a chemotherapeutic target.