DNA BINDING PROTEINS & REGULATION OF SURFACE GLYCOPROTEINS IN TRYPANOSOMA BRUCE

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 载体传播，原生生物寄生虫布氏锥虫是唯一已知的真核生物与多功能RNA聚合酶I，除了核糖体基因，转录基因编码寄生虫的主要细胞表面蛋白的变体表面糖蛋白（VSG）和原环素。在哺乳动物的血流中，VSG外套的抗原变异是寄生虫逃避免疫反应的手段，而原环素是有效建立蝇锥虫感染所必需的。此外，单等位基因VSG表达的极高效率对于血流锥虫是必不可少的，因为其沉默引起体外快速细胞周期停滞和从感染小鼠中清除寄生虫。在这里，我们描述了一种新的蛋白质复合物，识别I类启动子和I类转录是必不可少的，它由一个动力蛋白轻链和六个多肽，仅在锥虫寄生虫之间保守。根据复合物的基本转录功能，沉默一个关键亚基的表达对血流锥虫是致命的，并特别影响rRNA和VSG mRNA的丰度。该复合物被命名为I类转录因子A。这些结果发表：多功能I类转录在布氏锥虫依赖于一种新的蛋白质复合物。勃兰登堡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.