title: Transition of Plasmodium sporozoites into liver stage-like forms is regulated by the RNA binding protein Pumilio.
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.
authors.affiliation: Malaria Unit, Instituto de Medicina Molecular, Lisboa, Portugal.
authors.forename: Carina S S
authors.initials: CS
authors.lastname: Gomes-Santos
authors.forename: Joanna
authors.initials: J
authors.lastname: Braks
authors.forename: Miguel
authors.initials: M
authors.lastname: Prudêncio
authors.forename: Céline
authors.initials: C
authors.lastname: Carret
authors.forename: Ana Rita
authors.initials: AR
authors.lastname: Gomes
authors.forename: Arnab
authors.initials: A
authors.lastname: Pain
authors.forename: Theresa
authors.initials: T
authors.lastname: Feltwell
authors.forename: Shahid
authors.initials: S
authors.lastname: Khan
authors.forename: Andrew
authors.initials: A
authors.lastname: Waters
authors.forename: Chris
authors.initials: C
authors.lastname: Janse
authors.forename: Gunnar R
authors.initials: GR
authors.lastname: Mair
authors.forename: Maria M
authors.initials: MM
authors.lastname: Mota
mesh_terms: D000818:Animals; D000852:Anopheles / Q000469:parasitology; D020869:Gene Expression Profiling; D008099:Liver / Q000469:parasitology; D008288:Malaria / Q000469:parasitology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D010962:Plasmodium berghei / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism / Q000472:pathogenicity; D011499:Protein Processing, Post-Translational; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012469:Salivary Glands / Q000469:parasitology; D034101:Sporozoites / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D015800:Protozoan Proteins; D016601:RNA-Binding Proteins