The Cytoplasmic Ribosomal RNAs of Plusmodium spp T.F. McCutchan, J. Li, G.A. McConkey, M.J. Rogers and A.P. Waters zyxwvutsrqponmlkjihgfedcba Plasmodium spp zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA maintain several structuralZy distinct sets of ribosomai RNA genes whose expression is developmentally regulated. This feature sets them apart from ail other eu- karyotes studied to date. In this review, Thomas McCutchan, ]un Li, Glenn McConkey, John Rogers and Andy Waters give an account of the progress in our understanding of this unusual phenomenon as it relates to the biology of the parasite. They also outline an interesting turnabout in scien- tific direction involving the use of the parasite as an import- ant new model for the study of the eukayotic ribosome. The study of ribosomal RNAs (rRNAs) has attracted the attention of biologists because these molecules are central to defining the catalytic nature of the ribosome, the ubiquitous protein-nucleic acid complex that is basic to all living organisms. Not surprisingly, the rRNAs have nearly equivalent structure and function in all organisms and the gene families that encode these mol- ecules also display remarkable similarities in organiz- zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFE ational structure and transcriptional control. In contrast, Plasmodium spp each maintain a number of structurally distinct, nuclear encoded rRNAs whose transcription is developmentally controlled. As the rRNAs are central to the catalytic function of the ribosome, this suggests that there are characteristic differences in the process of protein synthesis at points during the life cycle of the parasite. The reasons why Plasmodium spp would differ from other eukaryotic organisms in the control of such a fundamental biological process are a mystery. Gaining an understanding of basic biochemical differ- ences between host and parasite is a common goal in parasitology, and progress in that direction, with re- gard to the cytoplasmic ribosome, is described below. A relationship between structure and function within broadly defined groups, eubacterial, mitochondrial and eukaryotic, can be preliminarily assessed on the basis of cross-species comparisons of rRNA secondary struc- ture utilizing functional information from the more accessible systemsi. Thus a well-characterized and ac- tive structure such as the peptidyl transferase site is seen in all the large subunit (LSU) rRNAs, although this activi tems. F urX has only been demonstrated in a few sys- er, the genomic organization of the multi- copy genes that encode these rRNAs, the rDNA units, may also have predictive value. As with the structure of the single unit, the overall organization of the rDNA units in eukaryotic organisms can be broadly categor- ized into only a few different organizational paradigms. Certain forms of genomic organization have biochemi- zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Themes McCutchan, Jun Li, Glenn McConkey and M. John Rogers are at the Growth and Development Section, Laboratory of Para sitic Diseases, National lnstltute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0425, USA. Andy Waters is at the Laboratory for Paraatology, Unlversrty of Leiden. Wassenaaneweg 62, PO Box 9605, 2300 RC Leiden, The Netherlands. Tel: + I 30 I 496 4 149, Fax: + I 30 I 402 0079, e-mail: mcutchan@helix.nih.gov cal ramifications leading to a central purpose and ad- vantage2. It seems likely that deviations from the stan- dard structure, control and arrangement of rRNA in Plasmodium reflect an adaption of this genus the better to exploit its biological niche. The cytoplasmic ribosomal genes of a number of species of Plasmodium have been analyzed, including those that infect humans, non-human primates, rodents, birds and lizards. Clearly, a number of features of their structure and transcriptional control are not only un- usual but characteristic of the genus Plasmodium. PIUS- modium spp also maintain plastid rDNA units encoded on the 35 kb circle and the split mitochondrial units on the 5 kb repeat, which will not be encompassed in this review but are reviewed elsewhere3,4. Much of the current comparative analysis of the nuclear encoded genes has centered on structural analysis of the small subunit rRNA (SSU rRNA) and further analysis of the large subunit, 5.8s and internal transcribed spacers should greatly add to the story. Genomic organization of rDNA units The single rDNA unit of Plasmodium is arranged in a standard fashion, with a copy of the SSU rRNA, an internal transcribed spacer (ITSl), the 5.8s rRNA, another internal transcribed spacer (ITS 2) and the large subunit rRNA (LSU rRNA) genes proceeding in a 5 to 3’ directions. No other coding areas have been con- firmed in any unit, although this may prove to be a productive area of investigation as it has been in other parasitic protozoa6. Some features of the genomic arrangement of rRNA genes of Plasmodium deserve mention because they are unique and may have considerable biological signifi- cance. The number of rDNA units within these or- ganisms is not characteristic of that found in most eukaryotic organisms. For exam le, most eukaryotic organisms have ribosomal genes & at are highly repeti- tive. They are referred to as ‘dosage response’ genes in that reduction in number has deleterious consequences, presumably because cellular requirements for rRNA are not being metz. In contrast, Plasmodium spp have only 4-8 genes7-n and most probably only one or two of the genes are being transcribed at any one time7. There- fore, any mutation occurring in a rRNA gene should have a leveraged effect. For example, a mutation in a single gene may affect 50% of the transcripts and re- sult in phenotypic changes of the magnitude seen in the ‘bobbed mutants’ of Drosophila, which are caused by large deletions of numerous rDNA genes (for review see Ref. 2). The fact that Plasmodium spp have only a few rR.NA genes being transcribed at any one time and no definable nucleolus must also indicate something unique about this organism’s transcriptional machin- ery and ribosome assembly process. Due to the rapid rate of growth of this parasitic protozoa during points of its development, considerable demand must be put on its synthetic machinery. This suggests that the 134 D zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA 1395 Fiiev~v ic,r~~e,fd 0 49 4758/95/$0950 Porosrtology Today, vol. I I, no. 4, I995