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Public Library of Science, PLoS Pathogens, 5(7), p. e1002046, 2011

DOI: 10.1371/journal.ppat.1002046

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Transition of Plasmodium sporozoites into liver stage-like forms is regulated by the RNA binding protein Pumilio

Journal article published in 2011 by Carina S. S. Gomes-Santos, Joanna Braks, Miguel Prudêncio, Céline Carret, Ana Rita Gomes ORCID, Arnab Pain, Theresa Feltwell, Shahid Khan, Andrew Waters, Chris Janse, Gunnar R. Mair ORCID, Maria M. Mota
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Many eukaryotic developmental and cell fate decisions that are effected post-transcriptionally involve RNA binding proteins as regulators of translation of key mRNAs. In malaria parasites (Plasmodium spp.), the development of round, non-motile and replicating exo-erythrocytic liver stage forms from slender, motile and cell-cycle arrested sporozoites is believed to depend on environmental changes experienced during the transmission of the parasite from the mosquito vector to the vertebrate host. Here we identify a Plasmodium member of the RNA binding protein family PUF as a key regulator of this transformation. In the absence of Pumilio-2 (Puf2) sporozoites initiate EEF development inside mosquito salivary glands independently of the normal transmission-associated environmental cues. Puf2- sporozoites exhibit genome-wide transcriptional changes that result in loss of gliding motility, cell traversal ability and reduction in infectivity, and, moreover, trigger metamorphosis typical of early Plasmodium intra-hepatic development. These data demonstrate that Puf2 is a key player in regulating sporozoite developmental control, and imply that transformation of salivary gland-resident sporozoites into liver stage-like parasites is regulated by a post-transcriptional mechanism. ; Fundação para a Ciência e Tecnologia ; British Council