The Wellcome Trust Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dow Street, DundeeDD1 5EH, UK.
Parasitology. 2021 Sep;148(10):1237-1253. doi: 10.1017/S0031182020002437. Epub 2021 Jan 7.
African trypanosomes are early divergent protozoan parasites responsible for high mortality and morbidity as well as a great economic burden among the world's poorest populations. Trypanosomes undergo antigenic variation in their mammalian hosts, a highly sophisticated immune evasion mechanism. Their nuclear organization and mechanisms for gene expression control present several conventional features but also a number of striking differences to the mammalian counterparts. Some of these unorthodox characteristics, such as lack of controlled transcription initiation or enhancer sequences, render their monogenic antigen transcription, which is critical for successful antigenic variation, even more enigmatic. Recent technological developments have advanced our understanding of nuclear organization and gene expression control in trypanosomes, opening novel research avenues. This review is focused on Trypanosoma brucei nuclear organization and how it impacts gene expression, with an emphasis on antigen expression. It highlights several dedicated sub-nuclear bodies that compartmentalize specific functions, whilst outlining similarities and differences to more complex eukaryotes. Notably, understanding the mechanisms underpinning antigen as well as general gene expression control is of great importance, as it might help designing effective control strategies against these organisms.
非洲锥虫是早期分化的原生动物寄生虫,在世界上最贫困的人群中造成高死亡率和发病率以及巨大的经济负担。锥虫在其哺乳动物宿主中经历抗原变异,这是一种高度复杂的免疫逃避机制。它们的核组织和基因表达调控机制具有一些常规特征,但也与哺乳动物有许多显著的差异。其中一些非传统的特征,如缺乏受控的转录起始或增强子序列,使得它们的单基因抗原转录更加神秘,这对于成功的抗原变异至关重要。最近的技术发展提高了我们对锥虫核组织和基因表达调控的理解,开辟了新的研究途径。本综述重点关注布氏锥虫的核组织及其对基因表达的影响,特别强调抗原表达。它突出了几个专门的亚核体,这些亚核体将特定的功能分隔开来,同时概述了与更复杂的真核生物的相似之处和不同之处。值得注意的是,了解抗原以及一般基因表达调控的机制非常重要,因为它可能有助于设计针对这些生物体的有效控制策略。