||African sleeping sickness, which is caused by the eukaryotic protozoan Trypanosoma brucei , is an epidemic in many African communities. RNA Polymerase II-dependent gene transcription in trypanosomes is unusual in many regards. Polycistronic transcripts are generated. There are very few introns. A 39-nucleotide capped spliced leader (SL) RNA is trans-spliced onto the 5' end of messages. The SL RNA gene is transcribed by RNA Polymerase II, and contains the only identified RNA Polymerase II promoter element to date. Recent studies found that the general transcription factor Tb TFIIB is essential for SL RNA gene transcription. A study of Tb TFIIB associating factors revealed a unique protein (TAF49, T FIIB a ssociating f actor, 49 kDA). This protein bears many hallmarks associated with transcription factors. The work herein demonstrates a tight interaction between Tb TFIIB and Tb TAF49, suggesting a role for Tb TAF49 in RNA polymerase II-dependent gene transcription. Furthermore, the Tb TAF49 protein is essential for trypanosome viability, as determined by RNA interference studies.