Mitochondrial RNA editing in Trypanoplasma borreli: new tools, new revelations

Gerasimov, Evgeny S., Afonin, Dmitry A., Korzhavina, Oksana A., Lukeš, Julius, Low, Ross, Hall, Neil ORCID: https://orcid.org/0000-0003-2808-0009, Tyler, Kevin ORCID: https://orcid.org/0000-0002-0647-8158, Yurchenko, Vyacheslav and Zimmer, Sara L. (2022) Mitochondrial RNA editing in Trypanoplasma borreli: new tools, new revelations. Computational and Structural Biotechnology Journal. ISSN 2001-0370

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Abstract

The kinetoplastids are unicellular flagellates that derive their name from their ‘kinetoplast’, a region within each flagellate’s single mitochondrion harboring its organellar genome of high DNA content. Some protein products of this mitochondrial genome are encoded as cryptogenes; their transcripts require editing to generate an open reading frame. This happens through an RNA editing process, whereby small regulatory guide RNAs direct the proper insertion and deletion of one or more uridines at each editing site within specific transcript regions. An accurate perspective of the mitochondrial DNA expansion of kinetoplastids and the evolution of their unique uridine insertion/deletion editing across the entire group has been difficult to achieve. Here, we resolved outstanding questions about the organization of the mitochondrial genome and its editing in the kinetoplastid Trypanoplasma borreli that is evolutionarily distant from the frequently-studied trypanosomatids. We find that its mitochondrial DNA consists of circular molecules of 42 kb that harbor the rRNA and mRNAs, and 17 different contigs of approximately 70 kb carrying an average of 23 putative guide RNA loci per contig. These contigs may be linear molecules; they contain repetitive termini. Our analysis uncovered a putative gRNA population with unique length and sequence parameters that is massive relative to the editing needs of this parasite. We validated or determined the sequence identity of each of the four edited mRNA species – including one coding for ATP synthase 6 that was previously thought to be missing. We utilized our computational methods to show that the T. borreli transcriptome includes a substantial number of transcripts with editing patterns not consistent with the identified product, a result of non-canonical editing. We also discovered that this species is more likely than other kinetoplastids to utilize uridine deletion to enforce amino acid conservation of cryptogene products, although deletion is still less common than insertion. Finally, in three tested kinetoplastid mitochondrial transcriptomes, uridine deletion is more common in the raw mitochondrial read population than it appears when the fully edited translationally competent mRNAs only are considered. We conclude that the organization of mitochondrial DNA across all kinetoplastids can be described as variations on several central themes. These themes include partitioned coding and repetitive regions of a circular molecule encoding mRNA and rRNA, and guide RNA loci positioned on a malleable population of multiple molecules that differ in relative abundance in different strains. Likewise, while all kinetoplastids possess the central mechanism of uridine insertion/deletion RNA editing, its output parameters are species-specific.

Item Type: Article
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Faculty of Science > School of Biological Sciences
Depositing User: LivePure Connector
Date Deposited: 17 Nov 2022 15:30
Last Modified: 17 Nov 2022 15:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/89920
DOI: 10.1016/j.csbj.2022.11.023

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