Prucca César G, Slavin Ileana, Quiroga Rodrigo, Elías Eliana V, Rivero Fernando D, Saura Alicia, Carranza Pedro G, Luján Hugo D
Laboratorio de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Católica de Córdoba, Córdoba X5004ASK, Argentina.
Nature. 2008 Dec 11;456(7223):750-4. doi: 10.1038/nature07585.
Giardia lamblia (also called Giardia intestinalis) is one of the most common intestinal parasites of humans. To evade the host's immune response, Giardia undergoes antigenic variation-a process that allows the parasite to develop chronic and recurrent infections. From a repertoire of approximately 190 variant-specific surface protein (VSP)-coding genes, Giardia expresses only one VSP on the surface of each parasite at a particular time, but spontaneously switches to a different VSP by unknown mechanisms. Here we show that regulation of VSP expression involves a system comprising RNA-dependent RNA polymerase, Dicer and Argonaute, known components of the RNA interference machinery. Clones expressing a single surface antigen efficiently transcribe several VSP genes but only accumulate transcripts encoding the VSP to be expressed. Detection of antisense RNAs corresponding to the silenced VSP genes and small RNAs from the silenced but not for the expressed vsp implicate the RNA interference pathway in antigenic variation. Remarkably, silencing of Dicer and RNA-dependent RNA polymerase leads to a change from single to multiple VSP expression in individual parasites.
蓝氏贾第鞭毛虫（也称为肠贾第虫）是人类最常见的肠道寄生虫之一。为了逃避宿主的免疫反应，贾第虫会发生抗原变异——这一过程使寄生虫能够引发慢性和复发性感染。在大约190个变体特异性表面蛋白（VSP）编码基因的库中，贾第虫在特定时间每个寄生虫表面仅表达一种VSP，但通过未知机制自发切换到不同的VSP。在这里，我们表明VSP表达的调控涉及一个由RNA依赖性RNA聚合酶、Dicer和Argonaute组成的系统，这些是RNA干扰机制的已知组成部分。表达单一表面抗原的克隆有效地转录了几个VSP基因，但仅积累编码要表达的VSP的转录本。检测与沉默的VSP基因相对应的反义RNA以及来自沉默而非表达的vsp的小RNA，表明RNA干扰途径参与了抗原变异。值得注意的是，Dicer和RNA依赖性RNA聚合酶的沉默导致单个寄生虫中从单一VSP表达转变为多个VSP表达。
