Abstract
Malaria is a mosquito-borne infectious disease of humans and other animals. It is caused by the parasitic protozoan, Plasmodium. Sporozoites, the infectious form of malaria parasites, are quiescent when they remain in the salivary glands of the Anopheles mosquito until transmission into a mammalian host. Metamorphosis of the dormant sporozoite to its active form in the liver stage requires transcriptional and translational regulations. Here, we summarize recent advances in the translational repression of gene expression in the malaria sporozoite. In sporozoites, many mRNAs that are required for liver stage development are translationally repressed. Phosphorylation of eukaryotic Initiation Factor 2α (eIF2α) leads to a global translational repression in sporozoites. The eIF2α kinase, known as Upregulated in Infectious Sporozoite 1 (UIS1), is dominant in the sporozoite. The eIF2α phosphatase, UIS2, is translationally repressed by the Pumilio protein Puf2. This translational repression is alleviated when sporozoites are delivered into the mammalian host.
Highlights
Plasmodium sporozoites are quiescent for several weeks in mosquito salivary glands while maintaining their infectivity
The transcriptional and translational profiles of sporozoites and pre-erythrocytic stage parasites display significant lags in protein abundance relative to mRNA abundance, due to a global translational repression caused by the phosphorylation of eukaryotic Initiation Factor 2α (eIF2α) in salivary gland sporozoites
Activating Transcription Factor 4 (ATF4), a transcriptional activator of genes involved in the integrated stress response, is preferentially translated when eIF2α is phosphorylated in mammalian cells (Figure 1A)
Summary
Plasmodium sporozoites are quiescent for several weeks in mosquito salivary glands while maintaining their infectivity. * Corresponding Author: Min Zhang, E-mail: Dr.Min.Zhang@gmail.com Sporozoites, the infectious form of malaria parasites, are quiescent when they remain in the salivary glands of the Anopheles mosquito until transmission into a mammalian host. Metamorphosis of the dormant sporozoite to its active form in the liver stage requires transcriptional and translational regulations.
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