Plasmodium species face dramatic but predictable environmental changes during their life cycles, to which they must respond. These changes vary in degree, affect transmission of parasites and perhaps even the distribution of parasite populations. For example, changes in ambient temperature, are reflected in the rate of protein synthesis and hence the growth rate. An understanding of growth rate is a key factor in predicting parasite success and designing measures to control the disease. We have previously shown that P. falciparum expresses different ribosomal RNAs during its developmental cycle and that the relative quantities of each varies according to the state of development. There are five complete rDNA units that encode three dramatically different rRNAs. The sequence encoding mature A type RNAs are nearly identical and are encoded on chromosomes 5 (A1) and 7 (A2). There are also two copies of the S type gene encoded on chromosomes 11 (S2) and 13 (S2). Another rDNA unit, which is expressed in gametocytes (S1), encodes another S type small subunit RNA but is paired with a large subunit RNA whose sequence is dramatically different from both the A and S types. There is also an incomplete rDNA unit on chromosome 8 containing only the 5.8S RNA and LSU RNA genes. Compensatory mutations in the LSU sequence appear to maintain the secondary structure of rRNAs, suggesting that there is selective pressure to maintain functionality. The expression profile for this unit has not been established. Control over the synthesis of each of the three different ribosomal RNAs of Plasmodium falciparum appears to be regulated by a different mechanism. During parasite development in blood, asexual forms of the parasite express the A type ribosomal RNA, while gametes express both A and S1 types. Expression of S2 type RNA is induced by a series of events associated with the temperature drop occurring during the mosquito blood feed. The abundance of S2 rRNA changes rapidly with changes in temperature. We have characterized a thermal-regulated non-coding RNA that is central to the control of S2rRNA production. Further we have shown that the stability of the S2 rRNA is very sensitive to temperature change. The combination of control over transcription and rapid breakdown of the mature rRNA at restrictive temperatures should enable turnover in the parasite protein synthesis machinery within a time frame and temperature range consistent with parasite development in mosquitoes. We also show that production of mature S2 rRNA is controlled by altering the temperature of the parasite in either the blood or in the mosquito regardless of its developmental state. This provides an approach to studying the control of Plasmodium ribosomal RNA production in vitro. The discovery means that the process and associated molecules are accessible to biochemical analysis, which would have otherwise been nearly impossible. In a natural environment, periodic up and downregulation of S2 ribosomes occurs during development of the parasite while in the mosquito. As the ambient temperatures rise, production of S2 ribosomes in the wild type parasite slows down and then ceases at temperatures approaching 37C. During the same period, the mature S2 rRNA is rapidly degraded. As the temperature decreases, S2 rRNA transcription is again activated, and the mature S2 rRNA is stable. Curiously, this cycle correlates with the cooler times of the day when the mosquito is active, dusk to dawn. In summary, P. falciparum goes through an asexual developmental cycle and produces gametocytes in humans in an environment where the temperature is relatively constant. Blood stage parasites are only exposed to dramatic temperature change briefly during transmission of the parasite from the human to the mosquito. The parasites development in the mosquito, however, occurs within a more variable range of temperatures. The environmental temperature affects the parasites growth rate. We have shown that the dosage of P. falciparum S RNA is regulated directly in response to temperature whether the parasite is in the mosquito or in red blood cells.
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