Abstract
UIS4 is a key protein component of the host-parasite interface in the liver stage of the rodent malaria parasite Plasmodium berghei and required for parasite survival after invasion. In the infectious sporozoite, UIS4 protein has variably been shown to be translated but also been reported to be translationally repressed. Here we show that uis4 mRNA translation is regulated by the P. berghei RNA binding protein Pumilio-2 (PbPuf2 or Puf2 from here on forward) in infectious salivary gland sporozoites in the mosquito vector. Using RNA immunoprecipitation we show that uis4 mRNA is bound by Puf2 in salivary gland sporozoites. In the absence of Puf2, uis4 mRNA translation is de-regulated and UIS4 protein expression upregulated in salivary gland sporozoites. Here, using RNA immunoprecipitation, we reveal the first Puf2-regulated mRNA in this parasite.
Highlights
RNA binding proteins play a key role in the temporal and spatial regulation of protein expression
The presence of an evolutionarily conserved RNA binding domain in P. berghei Puf2 [1] suggested that this protein might control the stability or translational efficiency of certain, yet unknown, transcripts that when deregulated resulted in the observed transformation event
UIS4 is critical for liver stage development of the rodent malaria parasite with a role in growth and maintenance of the parasitophorous vacuole membrane (PVM) but redundant for liver cell invasion [17, 20]
Summary
RNA binding proteins play a key role in the temporal and spatial regulation of protein expression. In the rodent malaria parasite Plasmodium berghei—a model for the human P. falciparum parasite—post-transcriptional gene regulatory mechanisms affect protein translation during the transmission of the parasite between the mosquito vector and a mammalian host which co-insides with major developmental changes [1,2,3,4,5,6,7,8] This for example includes RNA helicase DOZI and CITH-mediated translational repression in the intra-erythrocytic female gametocyte prior to uptake during a mosquito blood meal [2, 3, 8], through mRNA binding at either 5’ or 3’ untranslated region (UTR) [9]; global inhibition of translation by the eIF2alpha kinase IK2 in sporozoites [4]; as well as a role for the RNA binding protein Pumilio (Puf2) in the sporozoite [1, 5, 6]. Δpuf SGS are characterised by a rounding-up event which occurs only during the developmental program of the wildtype EEF and results from the breakdown of the inner membrane complex and subpellicular network
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