Abstract

BackgroundThe mitochondrial genome in the human malaria parasite Plasmodium falciparum is most unusual. Over half the genome is composed of the genes for three classic mitochondrial proteins: cytochrome oxidase subunits I and III and apocytochrome b. The remainder encodes numerous small RNAs, ranging in size from 23 to 190 nt. Previous analysis revealed that some of these transcripts have significant sequence identity with highly conserved regions of large and small subunit rRNAs, and can form the expected secondary structures. However, these rRNA fragments are not encoded in linear order; instead, they are intermixed with one another and the protein coding genes, and are coded on both strands of the genome. This unorthodox arrangement hindered the identification of transcripts corresponding to other regions of rRNA that are highly conserved and/or are known to participate directly in protein synthesis.Principal FindingsThe identification of 14 additional small mitochondrial transcripts from P. falcipaurm and the assignment of 27 small RNAs (12 SSU RNAs totaling 804 nt, 15 LSU RNAs totaling 1233 nt) to specific regions of rRNA are supported by multiple lines of evidence. The regions now represented are highly similar to those of the small but contiguous mitochondrial rRNAs of Caenorhabditis elegans. The P. falciparum rRNA fragments cluster on the interfaces of the two ribosomal subunits in the three-dimensional structure of the ribosome.SignificanceAll of the rRNA fragments are now presumed to have been identified with experimental methods, and nearly all of these have been mapped onto the SSU and LSU rRNAs. Conversely, all regions of the rRNAs that are known to be directly associated with protein synthesis have been identified in the P. falciparum mitochondrial genome and RNA transcripts. The fragmentation of the rRNA in the P. falciparum mitochondrion is the most extreme example of any rRNA fragmentation discovered.

Highlights

  • The human malaria parasite Plasmodium falciparum has a most unusual mitochondrial genome

  • While sequences similar to regions of large subunit (LSU) and small subunit (SSU) rRNAs are encoded by the P. falciparum mt genome, they are scattered across both strands of the genome, interspersed with each other and the protein coding genes, and correspond to small RNAs [3,4]

  • Plasmodium mt DNA Conservation Complete mt genome sequences are currently available for 25 species and one Plasmodium isolate collected from a mandrill, and for eight species in four related genera of hemosporidians (Table S1)

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Summary

Introduction

The human malaria parasite Plasmodium falciparum has a most unusual mitochondrial (mt) genome It consists of tandem repeats of a 5967 nt sequence which encodes open reading frames similar to the genes for cytochrome c oxidase subunits I and III (cox and cox3) and apocytochrome b (cob) of other organisms [1]. Previous analysis revealed that some of these transcripts have significant sequence identity with highly conserved regions of large and small subunit rRNAs, and can form the expected secondary structures. These rRNA fragments are not encoded in linear order; instead, they are intermixed with one another and the protein coding genes, and are coded on both strands of the genome. This unorthodox arrangement hindered the identification of transcripts corresponding to other regions of rRNA that are highly conserved and/or are known to participate directly in protein synthesis

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