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From cradle to grave: RNA biology in malaria parasites

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Abstract Malaria is caused by the unicellular apicomplexan parasites of the genus Plasmodium, some of which, including the major human parasite Plasmodium falciparum, have extreme genome compositions (A/T content > 80%). In this overview of RNA production, roles and degradation, we show that despite their unusual genome composition these parasites generally exhibit the standard eukaryotic features of these processes. Thus genes are monocistronic and transcribed by RNA polymerases that conform to the general categories of I, II, and III. Plasmodium spp. are unusual in that they possess structurally distinct rRNA genes that are expressed at different points in the complicated life cycle of the parasite. Transcription in blood stage asexual parasites follows a cascade consistent with a dependency upon plant‐like apetala 2 (AP2) DNA‐binding proteins. mRNA is transported to, translated and degraded in the cytoplasm and the transcription pattern is largely inflexible and responsive to temperature and glucose but not drugs. Furthermore, although Plasmodium spp. undertake controlled repression of mRNA species at a number of points in their life cycle only one mechanism, employed by female gametocytes (gamete precursor cells), is clear; it resembles that of metazoan female gametes, consisting of a complex of repression‐associated proteins in an architecture formed with the mRNA 5′ cap and dependent on U‐rich untranslated region (UTR) elements. Extensive antisense transcription has been documented resulting in the production of both short and long transcripts of generally unknown functional significance. This review attempts to summarize what is currently known about the biology of Plasmodium RNA. Copyright © 2010 John Wiley & Sons, Ltd. This article is categorized under: Translation > Translation Regulation RNA in Disease and Development > RNA in Disease RNA in Disease and Development > RNA in Development

Life cycle of Plasmodium spp. The life cycle is illustrated for a human infectious species but is typical for all species that infect mammals. The names of the different morphs of the parasite throughout the cycle are indicated. The parasite is haploid for its entire life cycle apart from the formation of the zygote (2n) and ookinete (4n). The fruits of post‐genome surveys of proteomes and transcriptomes are indicated in the figure and are best located at www.PlasmoDB.org. An estimate of the comprehensive nature of each study is indicated by the extent of shading of each ‘book’, an exhaustive study being completely colored (Reprinted with permission from Ref 96. Copyright 2006 Nature Publishing Group).

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Possible mode of recruitment of the exosome to mRNA substrates. (a) The exosome, a barrel like structure, can be recruited to mRNA substrates through specific mRNA–protein interactions. The Ski2–Ski3–Ski8 complex seems to be recruited to the exosome (subunits numbered 1–10, see Table 2 for IDs) through interactions with the cytoplasmic subunit Ski‐7. (b) In the case of ARE sequences, specific ARE‐binding proteins such as TTP seem to physically interact with the exosome and recruit it to the mRNA. The homologies with predicted genes in all complete genomes of Plasmodium spp. are such that with the exception of the TRAMP complex the mechanisms of RNA degradation are expected to be conserved, see also Table 2 (Reprinted with permission from Ref 88. Copyright 2004 Nature Publishing Group).

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RNA in Disease and Development > RNA in Disease
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