title: Alternative RNA editing produces a novel protein involved in mitochondrial DNA maintenance in trypanosomes.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA.
authors.forename: Torsten
authors.initials: T
authors.lastname: Ochsenreiter
authors.forename: Sedrick
authors.initials: S
authors.lastname: Anderson
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Wood
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hajduk
mesh_terms: 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
chemical_list: D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D003576:Electron Transport Complex IV; D017394:RNA, Guide, Kinetoplastida