Alarcon C M, Pedram M, Donelson J E
Department of Biochemistry, University of Iowa, Iowa City, Iowa 52242, USA.
J Biol Chem. 1999 Jun 11;274(24):16884-93. doi: 10.1074/jbc.274.24.16884.
Trypanosoma brucei undergoes antigenic variation by periodically switching the expression of its variant surface glycoprotein (VSG) genes (vsg) among an estimated 20-40 telomere-linked expression sites (ES), only one of which is fully active at a given time. We found that in bloodstream trypanosomes one ES is transcribed at a high level and other ESs are expressed at low levels, resulting in organisms containing one abundant VSG mRNA and several rare VSG RNAs. Some of the rare VSG mRNAs come from monocistronic ESs in which the promoters are situated about 2 kilobases upstream of the vsg, in contrast to the polycistronic ESs in which the promoters are located 45-60 kilobases upstream of the vsg. The monocistronic ES containing the MVAT4 vsg does not include the ES-associated genes (esag) that occur between the promoter and the vsg in polycistronic ESs. However, bloodstream MVAT4 trypanosomes contain the mRNAs for many different ESAGs 6 and 7 (transferrin receptors), suggesting that polycistronic ESs are partially active in this clone. To explain these findings, we propose a model in which both mono- and polycistronic ESs are controlled by a similar mechanism throughout the parasite's life cycle. Certain VSGs are preferentially expressed in metacyclic versus bloodstream stages as a result of differences in ESAG expression and the proximity of the promoters to the vsg and telomere.
布氏锥虫通过在大约20 - 40个与端粒相连的表达位点（ES）之间周期性地切换其可变表面糖蛋白（VSG）基因（vsg）的表达来进行抗原变异，在给定时间只有一个位点是完全活跃的。我们发现，在血流中的锥虫中，一个ES高水平转录，其他ES低水平表达，导致生物体含有一种丰富的VSG mRNA和几种罕见的VSG RNA。一些罕见的VSG mRNA来自单顺反子ES，其中启动子位于vsg上游约2千碱基处，这与多顺反子ES不同，多顺反子ES中的启动子位于vsg上游45 - 60千碱基处。包含MVAT4 vsg的单顺反子ES不包括在多顺反子ES中位于启动子和vsg之间的ES相关基因（esag）。然而，血流中的MVAT4锥虫含有许多不同的ESAG 6和7（转铁蛋白受体）的mRNA，这表明多顺反子ES在该克隆中部分活跃。为了解释这些发现，我们提出了一个模型，其中单顺反子和多顺反子ES在整个寄生虫生命周期中都由类似的机制控制。由于ESAG表达以及启动子与vsg和端粒的距离不同，某些VSG在循环后期与血流阶段中优先表达。
