Universal features of post-transcriptional gene regulation are critical for pla...

• Autor(es): Mair, Gunnar R. ; Lasonder, Edwin ; Garver, Lindsey S. ; Franke-Fayard, Blandine M. D. ; Carret, Céline K. ; Wiegant, Joop C. A. G. ; Dirks, Roeland W. ; Dimopoulos, George ; Janse, Chris J. ; Waters, Andrew P.
• Data: 2010
• Identificador Persistente: http://hdl.handle.net/10451/5358
• Origem: Repositório da Universidade de Lisboa
• Assunto(s): Post-transcriptional gene regulation; Plasmodium zygote; mRNA; Malaria; Mosquito infection
• Tipo de Documento: Artigo
• Idioma: Inglês

Descrição

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.