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Molecular and Cellular Biology, September 2008, p. 5595-5604, Vol. 28, No. 18
0270-7306/08/$08.00+0     doi:10.1128/MCB.00637-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Alternative RNA Editing Produces a Novel Protein Involved in Mitochondrial DNA Maintenance in Trypanosomes{triangledown} ,{dagger}

Torsten Ochsenreiter,{ddagger} Sedrick Anderson,{ddagger} Zachary A. Wood, and Stephen L. Hajduk*

Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia 30602

Received 19 April 2008/ Returned for modification 11 June 2008/ Accepted 27 June 2008

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.

* Corresponding author. Mailing address: Department of Biochemistry and Molecular Biology, University of Georgia, B129 Life Sciences Building, Athens, GA 30602. Phone: (706) 542-1676. Fax: (706) 542-0182. E-mail: shajduk{at}bmb.uga.edu

{triangledown} Published ahead of print on 7 July 2008.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} T. Ochsenreiter and S. Anderson contributed equally to this work.

Molecular and Cellular Biology, September 2008, p. 5595-5604, Vol. 28, No. 18
0270-7306/08/$08.00+0     doi:10.1128/MCB.00637-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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