Transcription of 'inactive' expression sites in African trypanosomes leadsto expression of multiple transferrin receptor RNAs in bloodstream forms

African trypanosomes express a heterodimeric transferrin receptor that medi ates iron uptake from the host bloodstream. The genes encoding the receptor , ESAG6 and ESAG7, are found at the beginning of VSG expression sites: thes e are telomeric, polycistronic transcription units that each terminate with a gene encoding a trypanosome Variant surface glycoprotein, VSG. Approxima tely 20 of these VSG expression sites are found in the trypanosome genome, but only one VSG is expressed at a time. The conventional view is that one expression site promoter is extremely active whereas the others are either inactive or show very low, poorly processive activity, and that all transfe rrin receptor molecules are encoded by the active expression site. The 3'-e nd of the ESAG6 gene is more than 5 kb from the promoter. We show here that 20% of ESAG6 mRNA originates from the 'inactive' expression sites. We sugg est that many expression site promoters in trypanosomes show low-level acti vity throughout the life cycle, and that transcription proceeds for at leas t 5 kb. This suggests a simplified model of VSG expression site control whe reby the only regulated event is the strong activation of a single expressi on site promoter in bloodstream forms. (C) 1999 Elsevier Science B.V. All r ights reserved.