PDF(Pubmed)
Abstract：
In malaria parasites, the regulation of mRNA translation, storage and degradation during development and life-stage transitions remains largely unknown. Here, we functionally characterized the DEAD-box RNA helicase PfDOZI in P. falciparum. Disruption of pfdozi enhanced asexual proliferation but reduced sexual commitment and impaired gametocyte development. By quantitative transcriptomics, we show that PfDOZI is involved in the regulation of invasion-related genes and sexual stage-specific genes during different developmental stages. PfDOZI predominantly participates in processing body-like mRNPs in schizonts but germ cell granule-like mRNPs in gametocytes to impose opposing actions of degradation and protection on different mRNA targets. We further show the formation of stress granule-like mRNPs during nutritional deprivation, highlighting an essential role of PfDOZI-associated mRNPs in stress response. We demonstrate that PfDOZI participates in distinct mRNPs to maintain mRNA homeostasis in response to life-stage transition and environmental changes by differentially executing post-transcriptional regulation on the target mRNAs.
摘要：
在疟疾寄生虫中，mRNA翻译的调节，在发育和生命阶段过渡期间的储存和退化在很大程度上仍然未知。这里,我们在功能上表征了恶性疟原虫中的DEAD-boxRNA解旋酶PfDOZI。pfdozi的破坏增强了无性增殖，但减少了性承诺和配子细胞发育受损。通过定量转录组学，我们表明，PfDOZI参与不同发育阶段的入侵相关基因和性阶段特异性基因的调节。PfDOZI主要参与处理分裂子体内的体样mRNPs，但参与处理配子细胞中的生殖细胞颗粒样mRNPs，以对不同的mRNA靶标施加相反的降解和保护作用。我们进一步显示了营养剥夺过程中应激颗粒样mRNPs的形成，强调PfDOZI相关mRNPs在应激反应中的重要作用。我们证明，PfDOZI参与不同的mRNPs，以通过对目标mRNA的差异执行转录后调控来维持mRNA稳态，以响应生命阶段的转变和环境变化。
