title: Differential Editosome Protein Function between Life Cycle Stages of Trypanosoma brucei.
abstract: Uridine insertion and deletion RNA editing generates functional mitochondrial mRNAs in Trypanosoma brucei. The mRNAs are differentially edited in bloodstream form (BF) and procyclic form (PF) life cycle stages, and this correlates with the differential utilization of glycolysis and oxidative phosphorylation between the stages. The mechanism that controls this differential editing is unknown. Editing is catalyzed by multiprotein ∼20S editosomes that contain endonuclease, 3'-terminal uridylyltransferase, exonuclease, and ligase activities. These editosomes also contain KREPB5 and KREPA3 proteins, which have no functional catalytic motifs, but they are essential for parasite viability, editing, and editosome integrity in BF cells. We show here that repression of KREPB5 or KREPA3 is also lethal in PF, but the effects on editosome structure differ from those in BF. In addition, we found that point mutations in KREPB5 or KREPA3 differentially affect cell growth, editosome integrity, and RNA editing between BF and PF stages. These results indicate that the functions of KREPB5 and KREPA3 editosome proteins are adjusted between the life cycle stages. This implies that these proteins are involved in the processes that control differential editing and that the 20S editosomes differ between the life cycle stages.
authors: From the Center for Infectious Disease Research, formerly known as Seattle Biomedical Research Institute, Seattle, Washington 98109.
authors: Suzanne M
authors: SM
authors: McDermott
authors: From the Center for Infectious Disease Research, formerly known as Seattle Biomedical Research Institute, Seattle, Washington 98109.
authors: Xuemin
authors: X
authors: Guo
authors: From the Center for Infectious Disease Research, formerly known as Seattle Biomedical Research Institute, Seattle, Washington 98109.
authors: Jason
authors: J
authors: Carnes
authors: From the Center for Infectious Disease Research, formerly known as Seattle Biomedical Research Institute, Seattle, Washington 98109 ken.stuart@cidresearch.org.
authors: Kenneth
authors: K
authors: Stuart
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001769:Blood / Q000469:parasitology; D002460:Cell Line; D004351:Drug Resistance / Q000235:genetics; D008018:Life Cycle Stages / Q000187:drug effects; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017393:RNA Editing; D043244:Ribonuclease III / Q000737:chemistry / Q000378:metabolism; D013752:Tetracycline / Q000494:pharmacology; D014346:Trypanosoma brucei brucei / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development* / Q000378:metabolism
chemical_list: D015800:Protozoan Proteins; D043244:Ribonuclease III; D013752:Tetracycline
keywords: RNA editing; Trypanosoma brucei; developmental regulation; differential editing; editosome; mitochondria; protein complex; protein domain; protein-protein interaction