Expression of the glycolytic enzymes enolase and lactate dehydrogenase during the early phase of Toxoplasma differentiation is regulated by an intron retention mechanism
Expression of the glycolytic enzymes enolase and lactate dehydrogenase during the early phase of Toxoplasma differentiation is regulated by an intron retention mechanism
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DOI：
10.1111/mmi.12999
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发表时间：
2015-06-01
影响因子：
3.6
通讯作者：
Di Cristina, Manlio
中科院分区：
文献类型：
--
作者：
Lunghi, Matteo;Galizi, Roberto;Di Cristina, Manlio
细胞内寄生虫刚地弓形虫在急性感染期间从快速复制的速殖子形式转化为在慢性感染期间持续存在于长寿细胞内的静止的成囊缓殖子阶段。缓殖子采取降低的代谢和缓慢的复制，同时等待机会在宿主内复发感染。这两个发育阶段之间的相互转换的特点是糖酵解同工酶的表达，在寄生虫代谢中发挥关键作用。寄生虫基因组编码以阶段特异性方式表达的乳酸脱氢酶（LDH 1和LDH 2）和烯醇化酶（ENO 1和ENO 2）的两种亚型。这些酶的不同同种型的表达允许T.弓形虫快速适应速殖子阶段的快速复制或缓殖子典型的静止生活方式所必需的各种代谢要求。在此，我们确定了未剪接形式的LDH和ENO转录在这两个寄生虫阶段之间的过渡期间产生的内含子保留机制，以迅速交换糖酵解异构体快速适应环境变化。我们还确定了ENO转录单位中的关键调控元件，揭示了ENO 2 5-非翻译区和ENO 2内含子之间的合作，沿着确定了ENO 1 3-非翻译区在阶段特异性表达中的作用。
The intracellular parasite Toxoplasma gondii converts from a rapidly replicating tachyzoite form during acute infection to a quiescent encysted bradyzoite stage that persists inside long-lived cells during chronic infection. Bradyzoites adopt reduced metabolism and slow replication while waiting for an opportunity to recrudesce the infection within the host. Interconversion between these two developmental stages is characterized by expression of glycolytic isoenzymes that play key roles in parasite metabolism. The parasite genome encodes two isoforms of lactate dehydrogenase (LDH1 and LDH2) and enolase (ENO1 and ENO2) that are expressed in a stage-specific manner. Expression of different isoforms of these enzymes allows T. gondii to rapidly adapt to diverse metabolic requirements necessary for either a rapid replication of the tachyzoite stage or a quiescent lifestyle typical of the bradyzoites. Herein we identified unspliced forms of LDH and ENO transcripts produced during transition between these two parasite stages suggestive of an intron retention mechanism to promptly exchange glycolytic isoforms for rapid adaptation to environmental changes. We also identified key regulatory elements in the ENO transcription units, revealing cooperation between the ENO2 5-untranslated region and the ENO2 intron, along with identifying a role for the ENO1 3-untranslated region in stage-specific expression.