A TFIIH Homologue Controls the Mutually Exclusive Expression of the Stage‐Specific Antigens of Trypanosoma brucei

Abstract

Antigenic variation in Trypanosoma brucei relies on a mono‐allelic control of the multiple variant surface glycoprotein (VSG) expression sites (ESs). A single ES is active in bloodstream forms (BF) and none are in insect‐specific procyclic forms (PF), where procyclin replaces the VSG. In PF, disrupting TbTFIIH by conditional RNAi of any of the Tbp44, TbXPD or TbXPB subunits, or by over‐expression of a TbXPD mutant, led to strong transcriptional stimulation in the beginning of the ESs. Both RNA elongation and mRNA production were up‐regulated. This effect was linked to inhibition of procyclin, and occurred irrespective of the various cellular phenotypes, some of which were lethal due to cell cycle arrest. In BF, stimulation of procyclin was linked to inhibition of the active ES. Thus, TbTFIIH is involved in the mutually exclusive expression of the VSG and procyclin transcription units, both of which are transcribed by RNA Pol I.