Author(s):
Gomes-Santos, Carina S. S.
; Braks, Joanna
; Prudêncio, Miguel
; Carret, Céline
; Gomes, Ana Rita
; Pain, Arnab
; Feltwell, Theresa
; Khan, Shahid
; Waters, Andrew
; Janse, Chris
; Mair, Gunnar R.
; Mota, Maria M.
Date: 2011
Persistent ID: http://hdl.handle.net/10316/15539
Origin: Estudo Geral - Universidade de Coimbra
Description
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