Translational repression of the cpw-wpc gene family in the malaria parasite Plasmodium

Handle URI:
http://hdl.handle.net/10754/613687
Title:
Translational repression of the cpw-wpc gene family in the malaria parasite Plasmodium
Authors:
Rao, Pavitra N.; Santos, Jorge M.; Pain, Arnab ( 0000-0002-1755-2819 ) ; Templeton, Thomas J.; Mair, Gunnar R.
Abstract:
The technical challenges of working with the sexual stages of the malaria parasite Plasmodium have hindered the characterization of sexual stage antigens in the quest for a successful malaria transmission-blocking vaccine. One such predicted and largely uncharacterized group of sexual stage candidate antigens is the CPW-WPC family of proteins. CPW-WPC proteins are named for a characteristic domain that contains two conserved motifs, CPxxW and WPC. Conserved across Apicomplexa, this family is also present earlier in the Alveolata in the free-living, non-parasitophorous, photosynthetic chromerids, Chromera and Vitrella. In P. falciparum and P. berghei blood stage parasites the transcripts of all nine cpw-wpc genes have been detected in gametocytes. RNA immunoprecipitation followed by reverse transcriptase-PCR reveals all P. berghei cpw-wpc transcripts to be bound by the translational repressors DOZI and CITH, and thus are likely under translational control prior to transmission from the rodent host to the mosquito vector in P. berghei. The GFP tagging of two endogenous P. berghei genes confirmed translational silencing in the gametocyte and translation in ookinetes. Establishing a luciferase transgene assay we show that the 3′ untranslated region of PF3D7_1331400 controls protein expression of this reporter in P. falciparum gametocytes. Our analyses suggest that cpw-wpc genes are translationally silenced in gametocytes across Plasmodium spp. and activated during ookinete formation and thus may have a role in transmission to the mosquito.
KAUST Department:
Pathogen Genomics Laboratory; Biological and Environmental Sciences and Engineering (BESE) Division
Citation:
Translational repression of the cpw-wpc gene family in the malaria parasite Plasmodium 2016 Parasitology International
Publisher:
Elsevier BV
Journal:
Parasitology International
Issue Date:
14-Jun-2016
DOI:
10.1016/j.parint.2016.06.007
Type:
Article
ISSN:
13835769
Sponsors:
The authors would like to thank Dr. Friedrich Frischknecht, Dr. Photini Sinnis, Dr. Alida Coppi, Dr. Kirk Deitsch, Dr. Cristina Bancells and Dr. Cristina Moreira for their suggestions and help with experiments. This work received financial support from Fundação para a Ciência e a Tecnologia (FCT) of the Portuguese Ministry of Science, Technology and High Education and the British Council; Jorge M. Santos was supported by an FCT Ph.D. Fellowship (SFRH/BD/63849/2009). Dr. Gunnar R. Mair was supported by FCT projectsPTDC/BIA-BCM/105610/2008 and PTDC/SAU-MIC/122082/2010. Dr. Thomas Templeton was supported by the NIH/NIAID grant 1R01AI080754-01 A1, the William Randolph Hearst Foundation, and a visiting professorship to the Institute of Tropical Medicine, Nagasaki University, Japan.
Additional Links:
http://linkinghub.elsevier.com/retrieve/pii/S138357691630068X
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Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorRao, Pavitra N.en
dc.contributor.authorSantos, Jorge M.en
dc.contributor.authorPain, Arnaben
dc.contributor.authorTempleton, Thomas J.en
dc.contributor.authorMair, Gunnar R.en
dc.date.accessioned2016-06-20T10:20:19Z-
dc.date.available2016-06-20T10:20:19Z-
dc.date.issued2016-06-14-
dc.identifier.citationTranslational repression of the cpw-wpc gene family in the malaria parasite Plasmodium 2016 Parasitology Internationalen
dc.identifier.issn13835769-
dc.identifier.doi10.1016/j.parint.2016.06.007-
dc.identifier.urihttp://hdl.handle.net/10754/613687-
dc.description.abstractThe technical challenges of working with the sexual stages of the malaria parasite Plasmodium have hindered the characterization of sexual stage antigens in the quest for a successful malaria transmission-blocking vaccine. One such predicted and largely uncharacterized group of sexual stage candidate antigens is the CPW-WPC family of proteins. CPW-WPC proteins are named for a characteristic domain that contains two conserved motifs, CPxxW and WPC. Conserved across Apicomplexa, this family is also present earlier in the Alveolata in the free-living, non-parasitophorous, photosynthetic chromerids, Chromera and Vitrella. In P. falciparum and P. berghei blood stage parasites the transcripts of all nine cpw-wpc genes have been detected in gametocytes. RNA immunoprecipitation followed by reverse transcriptase-PCR reveals all P. berghei cpw-wpc transcripts to be bound by the translational repressors DOZI and CITH, and thus are likely under translational control prior to transmission from the rodent host to the mosquito vector in P. berghei. The GFP tagging of two endogenous P. berghei genes confirmed translational silencing in the gametocyte and translation in ookinetes. Establishing a luciferase transgene assay we show that the 3′ untranslated region of PF3D7_1331400 controls protein expression of this reporter in P. falciparum gametocytes. Our analyses suggest that cpw-wpc genes are translationally silenced in gametocytes across Plasmodium spp. and activated during ookinete formation and thus may have a role in transmission to the mosquito.en
dc.description.sponsorshipThe authors would like to thank Dr. Friedrich Frischknecht, Dr. Photini Sinnis, Dr. Alida Coppi, Dr. Kirk Deitsch, Dr. Cristina Bancells and Dr. Cristina Moreira for their suggestions and help with experiments. This work received financial support from Fundação para a Ciência e a Tecnologia (FCT) of the Portuguese Ministry of Science, Technology and High Education and the British Council; Jorge M. Santos was supported by an FCT Ph.D. Fellowship (SFRH/BD/63849/2009). Dr. Gunnar R. Mair was supported by FCT projectsPTDC/BIA-BCM/105610/2008 and PTDC/SAU-MIC/122082/2010. Dr. Thomas Templeton was supported by the NIH/NIAID grant 1R01AI080754-01 A1, the William Randolph Hearst Foundation, and a visiting professorship to the Institute of Tropical Medicine, Nagasaki University, Japan.en
dc.language.isoenen
dc.publisherElsevier BVen
dc.relation.urlhttp://linkinghub.elsevier.com/retrieve/pii/S138357691630068Xen
dc.rightsNOTICE: this is the author’s version of a work that was accepted for publication in Parasitology International. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Parasitology International, 14 June 2016. DOI: 10.1016/j.parint.2016.06.007en
dc.subjectTranslational repressionen
dc.subjectCPW-WPCen
dc.subjectPlasmodiumen
dc.subjectmalariaen
dc.subjectgametocyteen
dc.subjectookineteen
dc.titleTranslational repression of the cpw-wpc gene family in the malaria parasite Plasmodiumen
dc.typeArticleen
dc.contributor.departmentPathogen Genomics Laboratoryen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.identifier.journalParasitology Internationalen
dc.eprint.versionPost-printen
dc.contributor.institutionDepartment of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, USAen
dc.contributor.institutionPrograms in Biochemistry, Cell, and Molecular Biology, Weill Graduate School of Medical Sciences of Cornell University, New York, NY 10065, USAen
dc.contributor.institutionInstituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028, Lisbon, Portugalen
dc.contributor.institutionGlobal Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, N20 W10 Kita-ku, Sapporo 001-0020, Japanen
dc.contributor.institutionDepartment of Protozoology, Institute of Tropical Medicine (NEKKEN), Nagasaki 852-8523, Japanen
dc.contributor.institutionParasitology, Department of Infectious Diseases, University of Heidelberg Medical School, Im Neuenheimer Feld 345, 69120 Heidelberg, Germanyen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorPain, Arnaben
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