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|Title: ||Universal features of post-transcriptional gene regulation are critical for plasmodium zygote development|
|Authors: ||Mair, Gunnar R.|
Garver, Lindsey S.
Franke-Fayard, Blandine M. D.
Carret, Céline K.
Wiegant, Joop C. A. G.
Dirks, Roeland W.
Janse, Chris J.
Waters, Andrew P.
|Keywords: ||Post-transcriptional gene regulation|
|Issue Date: ||Feb-2010|
|Publisher: ||PLoS - Public Library of Science|
|Citation: ||PLoS Pathogens | February 2010 | Volume 6 | Issue 2 | e1000767|
|Abstract: ||A universal feature of metazoan sexual development is the generation of oocyte P granules that withhold certain mRNA
species from translation to provide coding potential for proteins during early post-fertilization development. Stabilisation of
translationally quiescent mRNA pools in female Plasmodium gametocytes depends on the RNA helicase DOZI, but the
molecular machinery involved in the silencing of transcripts in these protozoans is unknown. Using affinity purification
coupled with mass-spectrometric analysis we identify a messenger ribonucleoprotein (mRNP) from Plasmodium berghei
gametocytes defined by DOZI and the Sm-like factor CITH (homolog of worm CAR-I and fly Trailer Hitch). This mRNP
includes 16 major factors, including proteins with homologies to components of metazoan P granules and archaeal
proteins. Containing translationally silent transcripts, this mRNP integrates eIF4E and poly(A)-binding protein but excludes P
body RNA degradation factors and translation-initiation promoting eIF4G. Gene deletion mutants of 2 core components of
this mRNP (DOZI and CITH) are fertilization-competent, but zygotes fail to develop into ookinetes in a female gametocytemutant
fashion. Through RNA-immunoprecipitation and global expression profiling of CITH-KO mutants we highlight CITH
as a crucial repressor of maternally supplied mRNAs. Our data define Plasmodium P granules as an ancient mRNP whose
protein core has remained evolutionarily conserved from single-cell organisms to germ cells of multi-cellular animals and
stores translationally silent mRNAs that are critical for early post-fertilization development during the initial stages of
mosquito infection. Therefore, translational repression may offer avenues as a target for the generation of transmission
blocking strategies and contribute to limiting the spread of malaria.|
|Peer Reviewed: ||yes|
|Appears in Collections:||IMM - Artigos em Revistas Internacionais|
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