High throughput sequencing revolution reveals conserved fundamentals of U-indel editing

Sara L. Zimmer, Rachel M. Simpson, Laurie K. Read

Research output: Contribution to journalReview articlepeer-review

8 Scopus citations

Abstract

Among Euglenozoans, mitochondrial RNA editing occurs in the diplonemids and in the kinetoplastids that include parasitic trypanosomes. Yet U-indel editing, in which open reading frames (ORFs) on mRNAs are generated by insertion and deletion of uridylates in locations dictated by guide RNAs, appears confined to kinetoplastids. The nature of guide RNA and edited mRNA populations has been cursorily explored in a surprisingly extensive number of species over the years, although complete sets of fully edited mRNAs for most kinetoplast genomes are largely missing. Now, however, high throughput sequencing technologies have had an enormous impact on what we know and will learn about the mechanisms, benefits, and final edited products of U-indel editing. Tools including PARERS, TREAT, and T-Aligner function to organize and make sense of U-indel mRNA transcriptomes, which are comprised of mRNAs harboring uridylate indels both consistent and inconsistent with translatable products. From high throughput sequencing data come arguments that partially edited mRNAs containing “junction regions” of noncanonical editing are editing intermediates, and conversely, arguments that they are dead-end products. These data have also revealed that the percent of a given transcript population that is fully or partially edited varies dramatically between transcripts and organisms. Outstanding questions that are being addressed include the prevalence of sequences that apparently encode alternative ORFs, diversity of editing events in ORF termini and 5′ and 3′ untranslated regions, and the differences that exist in this byzantine process between species. High throughput sequencing technologies will also undoubtedly be harnessed to probe U-indel editing's evolutionary origins. This article is categorized under: RNA Processing > RNA Editing and Modification RNA Evolution and Genomics > Computational Analyses of RNA.

Original languageEnglish (US)
Article numbere1487
JournalWiley Interdisciplinary Reviews: RNA
Volume9
Issue number5
DOIs
StatePublished - Sep 1 2018

Bibliographical note

Funding Information:
The authors would like to thank Vyacheslav Yurchenko, University of Ostrava, Ostrava, CZE, for assistance in discerning the identities of analyzed kinetoplastids presented in Figure 2, and Julius Lukeš, Czech Academy of Sciences, for critical reading of the manuscript. Final editing by members of the Zimmer lab was also appreciated. This work was supported by the American Heart Association (16SDG26420019 to S.L.Z.) and National Institutes of Health (AI061580 to L.K.R.).

Keywords

  • RNA editing core complex
  • RNA editing substrate binding complex
  • constructive neutral evolution
  • evolvability
  • parasitology

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