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A Plasmodium yoelii Mei2-Like RNA Binding Protein Is Essential for Completion of Liver Stage Schizogony

机译:疟原虫yoelii Mei2样RNA结合蛋白是肝分裂期必不可少的。

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Plasmodium parasites employ posttranscriptional regulatory mechanisms as their life cycle transitions between host cell invasion and replication within both the mosquito vector and mammalian host. RNA binding proteins (RBPs) provide one mechanism for modulation of RNA function. To explore the role of Plasmodium RBPs during parasite replication, we searched for RBPs that might play a role during liver stage development, the parasite stage that exhibits the most extensive growth and replication. We identified a parasite ortholog of the Mei2 (Meiosis inhibited 2) RBP that is conserved among Plasmodium species (PlasMei2) and exclusively transcribed in liver stage parasites. Epitope-tagged Plasmodium yoelii PlasMei2 was expressed only during liver stage schizogony and showed an apparent granular cytoplasmic location. Knockout of PlasMei2 (plasmei2?) in P. yoelii only affected late liver stage development. The P. yoelii plasmei2? liver stage size increased progressively until late in development, similar to wild-type parasite development. However, P. yoelii plasmei2? liver stage schizonts exhibited an abnormal DNA segregation phenotype and failed to form exoerythrocytic merozoites. Consequently the cellular integrity of P. yoelii plasmei2? liver stages became increasingly compromised late in development and the majority of P. yoelii plasmei2? underwent cell death by the time wild-type liver stages mature and release merozoites. This resulted in a complete block of P. yoelii plasmei2? transition from liver stage to blood stage infection in mice. Our results show for the first time the importance of a Plasmodium RBP in the coordinated progression of late liver stage schizogony and maturation of new invasive forms.
机译:疟原虫寄生虫利用转录后调节机制,因为它们的生命周期在蚊媒和哺乳动物宿主内宿主细胞入侵和复制之间过渡。 RNA结合蛋白(RBP)提供了一种调节RNA功能的机制。为了探索疟原虫RBPs在寄生虫复制中的作用,我们搜索了可能在肝阶段发育中发挥作用的RBPs,该阶段显示出最广泛的生长和复制。我们确定了 Mei2 (减数分裂被抑制2)RBP的一个寄生虫直系同源物,在疟原虫物种(PlasMei2)中是保守的,仅在肝期寄生虫中转录。抗原表位标记的约氏疟原虫PlasMei2仅在肝脏分裂期才表达,并显示出明显的颗粒状胞质位置。 yoelii中的 PlasMei2 plasmei2 )的敲除仅影响晚期肝阶段的发育。约氏疟原虫 plasmei2 的肝脏阶段大小逐渐增加直至发育后期,类似于野生型寄生虫的发育。然而,约氏疟原虫 plasmei2 肝阶段裂殖体表现出异常的DNA分离表型,并且不能形成胞外裂殖子裂殖子。因此,约氏疟原虫 plasmei2 肝阶段的细胞完整性在发育后期逐渐受到损害,并且大部分约氏疟原虫 plasmei2 当野生型肝脏成熟并释放裂殖子时,β就发生了细胞死亡。这导致小鼠约氏疟原虫 plasmei2 从肝阶段到血阶段感染的完全阻断。我们的结果首次显示了疟原虫RBP在晚期肝分裂症和新侵袭性形式的成熟过程中的协调作用。

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