RNA editing in trypanosomal parasites (232.1)

Abstract

RNA editing in Trypanosomes is a posttranscriptional process that recodes mitochondrial mRNAs by inserting and deleting uridylates, as specified by gRNAs. The polygenic pre‐mRNA and pre‐gRNA transcripts are processed by several multiprotein complexes; 20S editosomes that serially catalyze RNA cleavage, U addition or removal and ligation and other complexes that add U tails to gRNAs, associate cognate gRNAs and mRNAs and add mRNA poly (A/U) tails. The complexes and accessory factors discriminate among thousands of similar editing sites (ESs) and edit precisely producing the translated mRNAs. The discrimination employs three editosome variants that each have one of three related endonuclease/partner‐protein pairs and different editing site cleavage specificities. The edited mRNAs encode oxidative phosphorylation system components. However, the mRNAs are differentially edited between lifecycle stages by a mechanism that is not yet known. Consequently insect stage T. brucei has a complete oxidative phosphorylation system while the animal stage does not and generates energy by glycolysis. Regulation of RNA editing is integrated within the network of cellular processes that recalibrate metabolic processes and cell surface composition. The animal forms serially express variant surface glycoproteins (VSGs) resulting in antigenic variation while Procyclin surface proteins, not VSGs, are expressed in the insect stage. A future challenge is to elucidate how these multiple cellular processes are integrated. The discovery of editing led to the realization that genomic information can be recoded and the findings that multiple mechanisms of editing exist and are widespread. The exploration of its integration within cellular processes may provide other novel insights.