TbRGG2, an essential RNA editing accessory factor in two Trypanosoma brucei life cycle stages.
June 29th, 2008 | by admin |TbRGG2, an essential RNA editing accessory factor in two Trypanosoma brucei life cycle stages.
In the mitochondria of kinetoplastid protozoa, including Trypanosoma brucei, RNA editing inserts and/or deletes uridines from pre-mRNAs to produce mature mRNAs for translation. RNA editing is carried out by several related multiprotein complexes known as editosomes, which contain all the enzymatic components required for catalysis of editing. In addition, non-editosome accessory factors necessary for editing of specific RNAs have also been described. Here, we report the in vitro and in vivo characterization of the mitochondrial TbRGG2 protein (originally termed TbRGGm), and demonstrate that it acts as an editing accessory factor. TbRGG2 is an RNA binding protein with a preference for poly(U). TbRGG2 protein levels are upregulated 10-fold in procyclic form (PF) T. brucei compared to bloodstream forms (BFs). Nevertheless, the protein is essential for growth in both life cycle stages. TbRGG2 associates with RNase-sensitive and RNase-insensitive mitochondrial complexes, some of which co-sediment with editosomes. RNAi-mediated depletion of TbRGG2 in both PF and BF T. brucei leads to a dramatic decrease in pan-edited RNAs, and in some cases a corresponding increase in the pre-edited RNA. TbRGG2 downregulation also results in moderate stabilization of never-edited and minimally edited RNAs. Thus, our data are consistent with a model in which TbRGG2 is multi-functional, strongly facilitating the editing of pan-edited RNAs and modestly destabilizing minimally edited and never-edited RNAs. This is the first example of an RNA editing accessory factor that functions in the mammalian infective T. brucei life cycle stage.
Fisk JC, Ammerman ML, Presnyak V, Read LK.
Microbiology and Immunology, University at Buffalo, Buffalo, NY 14214.