The anatomy and transcription of a monocistronic expression site for a metacyclic variant surface glycoprotein gene in Trypanosoma brucei.
African trypanosomes evade the immune response of their mammalian hosts by switching the expression of their variant surface glycoprotein genes (vsg). The bloodstream trypanosome clone MVAT4 of Trypanosoma brucei rhodesiense expresses a metacyclic vsg as a monocistronic RNA from a promoter located 2 kilobases (kb) upstream of its start codon. Determination of 23 kb of sequence at the metacyclic variant antigen type 4 (MVAT) vsg expression site (ES) revealed an ES-associated gene (esag) 1 preceded by an ingi retroposon and an inverted region containing an unrelated vsg, short stretches of 70-bp repeats and a pseudo esag 3. Nuclear run-on experiments indicate that the 18-kb region upstream of the MVAT4 vsg promoter is transcriptionally silent. However, multiple members of different esag families are expressed from elsewhere in the genome. The MVAT4 vsg promoter is highly repressed in the procyclic stage, in contrast to the known polycistronic vsg ESs which undergo abortive transcription. Activation of the MVAT4 vsg ES occurs in situ without nucleotide sequence changes, although this monocistronic ES undergoes a pattern of base J modifications similar to that reported for the polycistronic ESs. The relative simplicity of the MVAT4 vsg ES and the uncoupled expression of the vsg and esags provide a unique opportunity for investigating the molecular mechanisms responsible for antigenic variation in African trypanosomes.
Pedram
M
M
Department of Biochemistry, University of Iowa, Iowa City, Iowa 52242, USA.
Donelson
J E
JE
D000818:Animals; D000940:Antigenic Variation; D001769:Blood / Q000469:parasitology; D002454:Cell Differentiation; D017124:Conserved Sequence; D018628:Gene Dosage; D005786:Gene Expression Regulation; D017125:Genes, Protozoan; D008040:Genetic Linkage; D008969:Molecular Sequence Data; D015800:Protozoan Proteins; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D018626:Retroelements; D016615:Telomere / Q000235:genetics; D014158:Transcription, Genetic; D014346:Trypanosoma brucei brucei / Q000166:cytology / Q000235:genetics*; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000235:genetics*
C099281:ESAG 1 protein, Trypanosoma; C119706:MVAT4 protein, Trypanosoma brucei; D015800:Protozoan Proteins; D018626:Retroelements; D014643:Variant Surface Glycoproteins, Trypanosoma