The structure of the large subunit rRNA expressed in blood stages of Plasmodium falciparum

Abstract

Here we present the sequence of the large subunit (LSU) rRNA expressed in blood-stage forms (and therefore A-type) of the malaria parasite, Plasmodium falciparum, from two different isolates. We determined the genomic sequence of a rRNA unit of the CAMP parasite strain from within the internal transcribed spacer 1 (ITS1) through the 5.8S rRNA gene, the ITS2 and the entire large subunit rRNA gene. We have also determined the corresponding sequence of the gene of the FVO strain by sequencing cDNA clones derived from blood-stage asexual parasites. Differences between the two were due to scattered point mutations in expansion segments of the mature rRNA regions. In addition to the point mutations, the rRNA genes from the two strains could be distinguished by the presence of a more complex polymorphism near the 3' end of the molecule. The most complex polymorphic form was localized on a single chromosome and found in only a subset of geographically distinct isolates. The sequences of the 5.8S rRNA unit and the LSU rRNA unit reported here can be logically assembled into a complete secondary structure which conforms to the standard structure conserved in all eukaryotic ribosomes. The construction of a model of secondary structure for the LSU rRNA has allowed the identification of phylogenetically conserved sequences involved in drug interaction with the ribosome, as well as those sequences involved in tertiary interactions within the rRNA itself.