Alternative RNA editing produces a novel protein involved in mitochondrial DNA maintenance in trypanosomes.
The mitochondrial genome of trypanosomes is composed of thousands of topologically interlocked circular DNA molecules that form the kinetoplast DNA (kDNA). Most genes encoded by the kDNA require a posttranscriptional modification process called RNA editing to form functional mRNAs. Here, we show that alternative editing of the mitochondrial cytochrome c oxidase III (COXIII) mRNA in Trypanosoma brucei produces a novel DNA binding protein, alternatively edited protein 1 (AEP-1). AEP-1 localizes to the region of the cell between the kDNA and the flagellum and purifies with the tripartite attachment complex, a structure believed to physically link the kDNA and flagellar basal bodies. Expression of the DNA binding domain of AEP-1 results in aberrant kDNA structure and reduced cell growth, indicating that AEP-1 is involved in the maintenance of the kDNA. Perhaps most important, our studies show a gain of function through an alternatively edited mRNA and, for the first time, provide a link between the unusual structure of the kDNA and RNA editing in trypanosome mitochondria.
Ochsenreiter
Torsten
T
Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA.
Anderson
Sedrick
S
Wood
Zachary A
ZA
Hajduk
Stephen L
SL
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010641:Phenotype; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017393:RNA Editing; D017394:RNA, Guide, Kinetoplastida / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014346:Trypanosoma brucei brucei / Q000166:cytology* / Q000235:genetics* / Q000378:metabolism
D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D003576:Electron Transport Complex IV; D017394:RNA, Guide, Kinetoplastida