Trypanosoma brucei: posttranscriptional control of the variable surface glycoprotein gene expression site.

Abstract

The arrest of variable surface glycoprotein (VSG) synthesis is one of the first events accompanying the differentiation of Trypanosoma brucei bloodstream forms into procyclic forms, which are characteristic of the insect vector. This is because of a very fast inhibition of VSG gene transcription which occurs as soon as the temperature is lowered. We report that this effect is probably not controlled at the level of transcription initiation, since the beginning of the VSG gene expression site, about 45 kilobases upstream from the antigen gene, remains transcribed in procyclic forms. The permanent activity of the promoter readily accounts for the systematic reappearance, upon return to the bloodstream form after cyclical transmission, of the antigen type present before passage to the tsetse fly. The abortive transcription of the VSG gene expression site appears linked to RNA processing abnormalities. Such posttranscriptional controls may allow the modulation of gene expression in a genome organized in large multigenic transcription units.

Transcription is initiated on silent variant surface glycoprotein expression sites despite monoallelic expression in Trypanosoma brucei

“…Previous experiments pointed to mixed conclusions. On the one hand, transcripts from inactive ESs could be detected in bloodstream clones and even in procyclic forms, which do not express VSG, suggesting that transcription initiation takes place in all ESs simultaneously (22)(23)(24)(25)(26)(27)(28)(29). On the other hand, experiments tagging ESs with antibiotic-resistance genes showed that RNA expression can be detected from two ES, although the expression was unstable (30).…”

A similar gene is shared by both the variant surface glycoprotein and procyclin gene transcription units of Trypanosoma brucei.

“…posttranscriptional level. We have found that both transcription promoters are active in the two parasite forms and that differential gene expression is achieved through modification of RNA elongation and stability (7,12,23,24). However, this has not been found by others for the procyclin gene promoter (19,30).…”

“…brucei bloodstream forms were from the AnTat 1.3A clone, and procyclic forms were derived from the AnTat 1.1B clone by in vitro transformation (23).…”

Genomic and transcriptional linkage of the genes for calmodulin, EF-hand 5 protein, and ubiquitin extension protein 52 in Trypanosoma brucei.

“…This control may include regulated expression from a single promoter or posttranscriptional control. Such posttranscriptional control has been suggested for phosphoglycerate kinase genes (14), the variable glycoprotein expression site (29), and aldolase genes (40) and may include differential processing (miniexon addition or polyadenylation) or inherent stabilities of the mature mRNAs.…”