# Stunning Intricacies of RNA Editing Complexes RECC, RESC, and REH2C: Functional Organization, Developmental Regulation, and Evolutionary History in Kinetoplastid Protists

**Authors:** Suzanne M. McDermott, Julius Lukeš, Laurie K. Read, Reza Salavati, Achim Schnaufer, Sara L. Zimmer, Jason Carnes, Alasdair Ivens, Naghmeh Poorinmohammad, Nicholas J. Savill, Dave Speijer, Ken Stuart, Kristína Záhonová, Poorya Mirzavand Borujeni, Zihao Chen, Cody Goode, Sunil Kumar Sharma, Lars O’Hara, Jorge Cruz‐Reyes

PMC · DOI: 10.1002/wrna.70037 · Wiley Interdisciplinary Reviews. RNA · 2026-02-25

## TL;DR

This paper explores RNA editing in kinetoplastid protists, focusing on the roles of three key complexes and how modern tools like AI help understand their function and evolution.

## Contribution

The paper highlights recent advances in understanding the functional organization and regulation of RNA editing complexes using modern computational tools.

## Key findings

- RNA editing in kinetoplastids involves three key complexes: RECC, RESC, and REH2C.
- Modern tools like AI are being used to study the holo-editosome's organization and evolution.
- RNA editing varies across species in terms of extent and gene organization.

## Abstract

RNA metabolism in kinetoplastid protists (Kinetoplastea), including trypanosomes and Leishmania, involves unique post‐transcriptional mitochondrial RNA editing that creates translatable mRNAs through uridine (U) insertions and deletions (U‐indels) directed by antisense guide RNAs (gRNAs). Like other biological processes that require specific RNA targeting, this system faces several challenges beyond coordinating its many components: assembling mRNA‐gRNA hybrids, recognizing hundreds of sites, and accurately distinguishing pre‐edited, partially edited, and fully edited transcripts in the mitochondrial environment. In parasites such as Trypanosoma brucei, significant energetic adaptations to different host environments also involve critical editing changes during development. The editing holoenzyme includes three molecular complexes and isoforms that carry most proteins: RNA Editing Catalytic Complexes (RECCs), which catalyze U‐indel cycles; RNA Editing Substrate Complexes (RESCs), which serve as scaffolds to coordinate the editing components; and the RNA Editing Helicase 2 Complex (REH2C), which contains key proteins involved in developmental editing regulation. However, more proteins and functions are being discovered. The editing system, best understood in 
T. brucei
, shows considerable evolutionary conservation in its core machinery; however, it varies in the extent of RNA editing and the organization of mitochondrial mRNA and gRNA genes across different species. Here we explore recent progress in our understanding of RNA editing and the growing use of modern computational tools, including artificial intelligence (AI) and structural methods, to examine function, organization, developmental regulation, and evolutionary aspects of this amazing system.

This article is categorized under:
RNA Interactions with Proteins and Other Molecules > RNA‐Protein ComplexesRNA Processing > RNA Editing and Modification

RNA Interactions with Proteins and Other Molecules > RNA‐Protein Complexes

RNA Processing > RNA Editing and Modification

U‐indel RNA editing targets mRNA:gRNA duplexes through three key complexes that collectively govern assembly, specificity, catalysis, and developmental regulation. Modern tools, including artificial intelligence, analyze the organization, dynamics, and evolution of the remarkable holo‐editosome, opening new avenues in RNA biology and therapy.

## Linked entities

- **Proteins:** recC (exodeoxyribonuclease V subunit gamma), resC (factor required for cytochrome c synthesis)
- **Species:** Trypanosoma brucei (taxon 5691), Leishmania (taxon 5658)

## Full-text entities

- **Diseases:** leishmanias (MESH:D007896), RECCs (MESH:D012327), HAT (MESH:D014353), infection (MESH:D007239)
- **Chemicals:** glutamic acid (MESH:D018698), carbon (MESH:D002244), oxygen (MESH:D010100), gold (MESH:D006046), metal (MESH:D008670), poly(A) (MESH:D011061), ATP (MESH:D000255), triphosphate (MESH:C005692), 5' triphosphate (-)
- **Species:** Trypanosoma cruzi (species) [taxon 5693], Trypanosoma congolense (species) [taxon 5692], Crithidia fasciculata (species) [taxon 5656], Leptomonas pyrrhocoris (species) [taxon 157538], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Trypanosoma mega (species) [taxon 71805], Euglena gracilis (species) [taxon 3039], Trypanosoma musculi (species) [taxon 71806], Perkinsela sp. (species) [taxon 1935466], Leishmania tarentolae (species) [taxon 5689], Cavenderia fasciculata (species) [taxon 261658], Drosophila melanogaster (fruit fly, species) [taxon 7227], Glossina (tsetse flies, genus) [taxon 7393], Trypanoplasma borreli (species) [taxon 5710], Homo sapiens (human, species) [taxon 9606], Leishmania major (species) [taxon 5664], Ichthyobodo (genus) [taxon 155202], Leishmania braziliensis (species) [taxon 5660], Trypanosoma brucei (species) [taxon 5691], Leishmania (subgenus) [taxon 38568], Vickermania ingenoplastis (species) [taxon 2720891], Vickermania spadyakhi (species) [taxon 2720892]
- **Cell lines:** A6 — Homo sapiens (Human), Tongue squamous cell carcinoma, Cancer cell line (CVCL_5985)

## Full text

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## Figures

11 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12936278/full.md

## References

262 references — full list in the complete paper: https://tomesphere.com/paper/PMC12936278/full.md

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Source: https://tomesphere.com/paper/PMC12936278