DNA BINDING PROTEINS & REGULATION OF SURFACE GLYCOPROTEINS IN TRYPANOSOMA BRUCE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 媒介传播的原生寄生虫布氏锥虫是已知的唯一具有多功能RNA聚合酶I的真核生物，除了核糖体基因外，它还转录编码这种寄生虫的主要细胞表面蛋白--变种表面糖蛋白(VSG)和原环素的基因。在哺乳动物的血液中，VSG外壳的抗原性变化是寄生虫逃避免疫反应的手段，而原环素是有效建立苍蝇锥虫感染所必需的。此外，单等位基因VSG的异常高效表达对血流锥虫是必不可少的，因为它的沉默在体外导致细胞周期快速停止，并从感染的小鼠身上清除寄生虫。在这里，我们描述了一种新的蛋白质复合体，它识别I类启动子，是I类转录所必需的；它由动力蛋白轻链和六个仅在锥虫寄生虫中保守的多肽组成。根据该复合体的基本转录功能，沉默一个关键亚单位的表达对血流锥虫是致命的，并特异性地影响rRNA和VSG mRNA的丰度。该复合体被命名为I类转录因子A。这些结果已发表：布氏锥虫多功能I类转录依赖于一种新的蛋白质复合体。Brandenburg J，Schimanski B，Nogoceke E，Nguyen TN，Padovan JC，Chait BT，Cross GA，G？NZL A。 EMBO J.2007 26(23)：4856-66.

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The vector-borne, protistan parasite Trypanosoma brucei is the only known eukaryote with a multifunctional RNA polymerase I that, in addition to ribosomal genes, transcribes genes encoding the parasite's major cell-surface proteins-the variant surface glycoprotein (VSG) and procyclin. In the mammalian bloodstream, antigenic variation of the VSG coat is the parasite's means to evade the immune response, while procyclin is necessary for effective establishment of trypanosome infection in the fly. Moreover, the exceptionally high efficiency of mono-allelic VSG expression is essential to bloodstream trypanosomes since its silencing caused rapid cell-cycle arrest in vitro and clearance of parasites from infected mice. Here we describe a novel protein complex that recognizes class I promoters and is indispensable for class I transcription; it consists of a dynein light chain and six polypeptides that are conserved only among trypanosomatid parasites. In accordance with an essential transcriptional function of the complex, silencing the expression of a key subunit was lethal to bloodstream trypanosomes and specifically affected the abundance of rRNA and VSG mRNA. The complex was dubbed class I transcription factor A. These results were published: Multifunctional class I transcription in Trypanosoma brucei depends on a novel protein complex. Brandenburg J, Schimanski B, Nogoceke E, Nguyen TN, Padovan JC, Chait BT, Cross GA, G¿nzl A. EMBO J. 2007 26(23):4856-66.