RNA editing in trypanosomes

Abstract

The nucleotide sequence of mitochondrial pre-mRNAs in trypanosomes is posttranscriptionally edited by the insertion and deletion of uridylate (U) residues. In some RNAs editing is limited to small sections but in African trypanosomes, such as Trypanosoma brucei, 9 of the 18 known mitochondrial mRNAs are created by massive editing which can produce more than 50% of the coding sequence. In all cases, however, RNA editing is a key event in gene expression during which translatable RNAs are generated. The information for the editing process and possibly also the inserted Us are provided by small guide RNAs, which are encoded in both the maxicircle and minicircle components of the trypanosome mitochondrial DNA. Current models of editing are largely based on the characteristics of partially edited RNAs and on the occurrence in vivo and the possibility of synthesis in vitro of chimeric molecules in which a guide RNA is covalently linked through its 3' oligo(U) tail to an editing site in pre-mRNA. In this paper, I will review the research in this rapidly growing field and illustrate how different interpretations of the available data can lead to different views of the mechanism and the biochemistry of the editing process.

Leishmania tarentolae contains distinct cytosolic and mitochondrial glutaminyl–tRNA synthetase activities

“…Nowhere else in nature has a comparable structure been found. In addition, many mitochondrial genes in trypanosomatids represent cryptogenes, whose transcripts have to be extensively edited to become functional mRNAs (9). RNA editing was shown to be mediated by short RNAs, called guide RNAs (30), which have not been found in mitochondria of any other organism.…”

“…tarentolae belongs to the earliest diverging cells in eukaryotic evolution that have mitochondria (7). This is illustrated by a number of unique features of their mitochondria, including a bipartite, topologically interlocked genome, guide RNA-mediated RNA editing, and the lack of mitochondrial tRNA genes (8,9). Mitochondrial biogenesis in trypanosomatids therefore not only involves import of proteins, as in all other eukaryotes, but also import of the whole set of nuclearly encoded mitochondrial tRNAs (10)(11)(12)(13).…”

Detection of the Mitochondrially Encoded Cytochrome cOxidase Subunit I in the Trypanosomatid Protozoan Leishmania tarentolae

“…The loss of COI seems to be complete, because no signal can be detected on the corresponding Western blots. 3 After visualization of COI, the putative monomeric spot was blotted, and we could determine eleven of the twelve N-terminal residues. A match was found with the sequence predicted from the corresponding kinetoplast mRNA.…”

“…The encoded proteins include subunits I, II, and III (COI, 1 COII, and COIII) of cytochrome c oxidase (respiratory complex IV), apocytochrome b of ubiquinol-cytochrome c oxidoreductase (complex III), subunit 6 of oligomycin-sensitive ATPase (complex V), several subunits of NADH dehydrogenase (complex I), ribosomal protein S12, and a number of putative proteins with unknown function. Several of these proteins can only be synthesized if the corresponding mRNAs are posttranscriptionally "edited" by insertion and deletion of uridylate residues, a unique process that in extreme cases is capable of creating an entire reading frame out of a cryptic pre-mRNA sequence (3)(4)(5)(6).…”

The mechanism of U insertion/deletion RNA editing in kinetoplastid mitochondria

“…This unusual RNA modification process (5) involves the insertion and, to a lesser extent, the deletion of U residues from transcripts of maxicircle 'cryptogenes' (6)(7)(8)(9)(10)(11). The extent of editing varies from a few Us at a few adjacent sites to hundreds of Us at hundreds of sites over the entire gene ('pan-editing') (12).…”