Default Pathway of var2csa Switching and Translational Repression in Plasmodium falciparum

作者: Bobo W. Mok , Ulf Ribacke , Niloofar Rasti , Fred Kironde , Qijun Chen

DOI: 10.1371/JOURNAL.PONE.0001982

关键词: RNAGeneticsAntigenic variationPlasmodium falciparumGene silencingHeterochromatinGene expression profilingGeneRegulation of gene expressionBiology

摘要: Antigenic variation is a subtle process of fundamental importance to the survival microbial pathogen. In Plasmodium falciparum malaria, PfEMP1 major variable antigen and adhesin expressed at surface infected erythrocyte, which encoded for by members family 60 var-genes. Peri-nuclear repositioning epigenetic mechanisms control their mono-allelic expression. The switching depends in part on transition rates short-lived immune responses shared minor epitopes. Here we show var-genes switch common gene that highly transcribed, but sparsely translated into not erythrocyte surface. Highly clonal adhesive P. falciparum, distinct corresponding PfEMP1s onset, were propagated without enrichment or panning. parasites successively spontaneously switched transcribe var-gene (var2csa) matched loss expression host cell-binding. var2csa repositioned peri-nuclear area upon activation, away from telomeric clusters heterochromatin spliced, full-length RNA. Despite abundant transcripts, level intracellular was low suggesting post-transcriptional partake protein vivo, off-switching translational repression may constitute one pathway, among others, coordinating

参考文章(47)
Michael F. Duffy, Aphrodite Caragounis, Rintis Noviyanti, Helen M. Kyriacou, Ee Ken Choong, Katja Boysen, Julie Healer, J. Alexandra Rowe, Malcolm E. Molyneux, Graham V. Brown, Stephen J. Rogerson, Transcribed var Genes Associated with Placental Malaria in Malawian Women Infection and Immunity. ,vol. 74, pp. 4875- 4883 ,(2006) , 10.1128/IAI.01978-05
Ali Salanti, Trine Staalsoe, Thomas Lavstsen, Anja T. R. Jensen, M. P. Kordai Sowa, David E. Arnot, Lars Hviid, Thor G. Theander, Selective upregulation of a single distinctly structured var gene in chondroitin sulphate A-adhering Plasmodium falciparum involved in pregnancy-associated malaria Molecular Microbiology. ,vol. 49, pp. 179- 191 ,(2003) , 10.1046/J.1365-2958.2003.03570.X
A. Scherf, R. Hernandez-Rivas, P. Buffet, E. Bottius, C. Benatar, B. Pouvelle, J. Gysin, M. Lanzer, Antigenic variation in malaria: in situ switching, relaxed and mutually exclusive transcription of var genes during intra‐erythrocytic development in Plasmodium falciparum The EMBO Journal. ,vol. 17, pp. 5418- 5426 ,(1998) , 10.1093/EMBOJ/17.18.5418
Mirjam Kaestli, Ian A. Cockburn, Alfred Cortés, Kay Baea, J. Alexandra Rowe, Hans‐Peter Beck, Virulence of Malaria Is Associated with Differential Expression of Plasmodium falciparum var Gene Subgroups in a Case-Control Study The Journal of Infectious Diseases. ,vol. 193, pp. 1567- 1574 ,(2006) , 10.1086/503776
Richard MR Coulson, Neil Hall, Christos A Ouzounis, Comparative Genomics of Transcriptional Control in the Human Malaria Parasite Plasmodium falciparum Genome Research. ,vol. 14, pp. 1548- 1554 ,(2004) , 10.1101/GR.2218604
Alexander G. Maier, Melanie Rug, Matthew T. O'Neill, James G. Beeson, Matthias Marti, John Reeder, Alan F. Cowman, Skeleton-binding protein 1 functions at the parasitophorous vacuole membrane to traffic PfEMP1 to the Plasmodium falciparum–infected erythrocyte surface Blood. ,vol. 109, pp. 1289- 1297 ,(2007) , 10.1182/BLOOD-2006-08-043364
Benoit Gamain, Adama R. Trimnell, Christine Scheidig, Artur Scherf, Louis H. Miller, Joseph D. Smith, Identification of Multiple Chondroitin Sulfate A (CSA)–Binding Domains in the var2CSA Gene Transcribed in CSA-Binding Parasites The Journal of Infectious Diseases. ,vol. 191, pp. 1010- 1013 ,(2005) , 10.1086/428137
Ali Salanti, Madeleine Dahlbäck, Louise Turner, Morten A Nielsen, Lea Barfod, Pamela Magistrado, Anja TR Jensen, Thomas Lavstsen, Michael F Ofori, Kevin Marsh, Lars Hviid, Thor G Theander, None, Evidence for the involvement of VAR2CSA in pregnancy-associated malaria Journal of Experimental Medicine. ,vol. 200, pp. 1197- 1203 ,(2004) , 10.1084/JEM.20041579
P. Horrocks, R. Pinches, Z. Christodoulou, S. A. Kyes, C. I. Newbold, Variable var transition rates underlie antigenic variation in malaria Proceedings of the National Academy of Sciences of the United States of America. ,vol. 101, pp. 11129- 11134 ,(2004) , 10.1073/PNAS.0402347101
Mirjam Kaestli, Alfred Cortes, Moses Lagog, Michael Ott, Hans‐Peter Beck, Longitudinal Assessment of Plasmodium falciparum var Gene Transcription in Naturally Infected Asymptomatic Children in Papua New Guinea The Journal of Infectious Diseases. ,vol. 189, pp. 1942- 1951 ,(2004) , 10.1086/383250