Nucleic Acids Research Advance Access originally published online on April 20, 2009
Nucleic Acids Research 2009 37(11):3788-3798; doi:10.1093/nar/gkp239
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Nucleic Acids Research, 2009, Vol. 37, No. 11 3788-3798
© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Molecular genetics and comparative genomics reveal RNAi is not functional in malaria parasites
1The Walter & Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia, 2Instituto de Medicina Molecular, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal, 3Department of Parasitology, Centre of Infectious Diseases, Leiden University Medical Centre, Leiden, The Netherlands, 4Division of Infection and Immunity, Institute of Biomedical Life Sciences & Wellcome Centre for Molecular Parasitology, Glasgow Biomedical Research Centre, University of Glasgow, G12 8TA, Scotland, UK, 5Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne 3004 and 6Deakin University, Waurn Ponds, Victoria 3217, Australia
*To whom correspondence should be addressed. Tel: +61 3 5227 2923; Fax: +61 3 5227 2945; Email: taniad{at}deakin.edu.au
Received March 9, 2009. Revised March 30, 2009. Accepted March 30, 2009.
Techniques for targeted genetic disruption in Plasmodium, the causative agent of malaria, are currently intractable for those genes that are essential for blood stage development. The ability to use RNA interference (RNAi) to silence gene expression would provide a powerful means to gain valuable insight into the pathogenic blood stages but its functionality in Plasmodium remains controversial. Here we have used various RNA-based gene silencing approaches to test the utility of RNAi in malaria parasites and have undertaken an extensive comparative genomics search using profile hidden Markov models to clarify whether RNAi machinery exists in malaria. These investigative approaches revealed that Plasmodium lacks the enzymology required for RNAi-based ablation of gene expression and indeed no experimental evidence for RNAi was observed. In its absence, the most likely explanations for previously reported RNAi-mediated knockdown are either the general toxicity of introduced RNA (with global down-regulation of gene expression) or a specific antisense effect mechanistically distinct from RNAi, which will need systematic analysis if it is to be of use as a molecular genetic tool for malaria parasites.
Present address: Dina Vlachou, Division of Cell and Molecular Biology, Department of Life Sciences, Imperical College London, UK.
The authors wish it to be known that, in their opinion, the first three authors should be regarded as joint First Authors.
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