RNA Editing Mechanisms in Kinetoplastid Mitochondria

Kinetoplastid protozoa possess a uniquely elaborate mitochondrial genome, comprising a network of maxicircles and minicircles that encode transcripts requiring extensive uridine insertion/deletion (U-indel) editing. This process transforms pre-mRNAs into functional transcripts by the precise addition or removal of uridines, guided by small non-coding RNAs (guide RNAs or gRNAs) and catalysed by multi-protein editosome complexes. Editosomes contain core enzymatic modules for cleavage, uridine insertion or deletion and ligation, and they associate dynamically with accessory factors and RNA helicases that ensure editing fidelity and regulate developmental stage specificity. Certain transcripts undergo “pan-editing”, wherein nearly the entire coding region is reconstructed through successive gRNA-directed cycles, while others require only limited modification. Molecular insights reveal that RNA secondary structure, protein–RNA interactions and co-evolving protein domains act in concert to coordinate substrate recognition and progression through editing cascades. Beyond basic biology, this pathway represents an attractive drug target for trypanosomatid infections, since humans lack analogous U-indel editing systems. Recent advances have illuminated the interplay between editing machinery components, the evolution of editing site selection and opportunities for small-molecule inhibition.

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RNA Editing Mechanisms in Kinetoplastid Mitochondria publication trend

The graph below shows the total number of articles in rna editing mechanisms in kinetoplastid mitochondria across all publications each year (not limited to Nature Index journals).

Technical terms

Guide RNA (gRNA): A small non-coding RNA that base-pairs with pre-mRNA to specify sites of uridine insertion or deletion.

Editosome: A multi-protein complex that catalyses sequential RNA cleavage, uridine insertion/deletion and ligation during mitochondrial RNA editing.

U-indel editing: The post-transcriptional process of inserting or deleting uridines within mitochondrial transcripts.

Pan-editing: Extensive U-indel editing that reconstructs nearly the entire coding sequence of a pre-mRNA.

Pre-edited mRNA: The initial mitochondrial transcript containing frameshifts and incomplete codons that require U-indel editing.

References

1. Trypanosome RNA helicase KREH2 differentially controls non-canonical editing and putative repressive structure via a novel proposed ‘bifunctional’ gRNA in mRNA A6. Nucleic Acids Research (2023).
2. Hydrophobicity-Driven Increases in Editing in Mitochondrial mRNAs during the Evolution of Kinetoplastids. Molecular Biology and Evolution (2023).
3. High-throughput screening of compounds targeting RNA editing in Trypanosoma brucei: Novel molecular scaffolds with broad trypanocidal effects. Biochemical Pharmacology (2023).