Universal features of post-transcriptional gene regulation are critical for plasmodium zygote development
Autor(a) principal: | |
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Data de Publicação: | 2010 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10451/5358 |
Resumo: | 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. |
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Universal features of post-transcriptional gene regulation are critical for plasmodium zygote developmentPost-transcriptional gene regulationPlasmodium zygotemRNAMalariaMosquito infectionA 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.This study was supported by a BioMalPar Network of Excellence and a Wellcome Trust Functional Genomics Initiative grant to APW and a Netherlands Genomics Initiative HORIZON Project (050-71-061) to GRM; CKC is recipient of an Fundação para a Ciência e a Tecnologia (SFRH/BPD/40965/2007) fellowship. APW is a Wellcome Trust Principal Research Fellow. This work has been supported by the National Institutes of Health/National Institute for Allergy and Infectious Disease 1R01AI061576-01A1, the Johns Hopkins Malaria Research Institute and Johns Hopkins School of Public Health (GD). LSG was supported by a National Science Foundation (NSF) fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.PLoS - Public Library of ScienceRepositório da Universidade de LisboaMair, Gunnar R.Lasonder, EdwinGarver, Lindsey S.Franke-Fayard, Blandine M. D.Carret, Céline K.Wiegant, Joop C. A. G.Dirks, Roeland W.Dimopoulos, GeorgeJanse, Chris J.Waters, Andrew P.2012-02-22T11:54:57Z2010-022010-02-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/5358engPLoS Pathogens | February 2010 | Volume 6 | Issue 2 | e10007671553-7366info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T15:47:00Zoai:repositorio.ul.pt:10451/5358Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:30:44.470269Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Universal features of post-transcriptional gene regulation are critical for plasmodium zygote development |
title |
Universal features of post-transcriptional gene regulation are critical for plasmodium zygote development |
spellingShingle |
Universal features of post-transcriptional gene regulation are critical for plasmodium zygote development Mair, Gunnar R. Post-transcriptional gene regulation Plasmodium zygote mRNA Malaria Mosquito infection |
title_short |
Universal features of post-transcriptional gene regulation are critical for plasmodium zygote development |
title_full |
Universal features of post-transcriptional gene regulation are critical for plasmodium zygote development |
title_fullStr |
Universal features of post-transcriptional gene regulation are critical for plasmodium zygote development |
title_full_unstemmed |
Universal features of post-transcriptional gene regulation are critical for plasmodium zygote development |
title_sort |
Universal features of post-transcriptional gene regulation are critical for plasmodium zygote development |
author |
Mair, Gunnar R. |
author_facet |
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. |
author_role |
author |
author2 |
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. |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
dc.contributor.author.fl_str_mv |
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. |
dc.subject.por.fl_str_mv |
Post-transcriptional gene regulation Plasmodium zygote mRNA Malaria Mosquito infection |
topic |
Post-transcriptional gene regulation Plasmodium zygote mRNA Malaria Mosquito infection |
description |
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. |
publishDate |
2010 |
dc.date.none.fl_str_mv |
2010-02 2010-02-01T00:00:00Z 2012-02-22T11:54:57Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/5358 |
url |
http://hdl.handle.net/10451/5358 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
PLoS Pathogens | February 2010 | Volume 6 | Issue 2 | e1000767 1553-7366 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
PLoS - Public Library of Science |
publisher.none.fl_str_mv |
PLoS - Public Library of Science |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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