Trypanosome RNA helicase KREH2 differentially controls non-canonical editing and putative repressive structure via a novel proposed 'bifunctional' gRNA in mRNA A6. Academic Article uri icon


  • U-insertion/deletion (U-indel) RNA editing in trypanosome mitochondria is directed by guide RNAs (gRNAs). This editing may developmentally control respiration in bloodstream forms (BSF) and insect procyclic forms (PCF). Holo-editosomes include the accessory RNA Editing Substrate Binding Complex (RESC) and RNA Editing Helicase 2 Complex (REH2C), but the specific proteins controlling differential editing remain unknown. Also, RNA editing appears highly error prone because most U-indels do not match the canonical pattern. However, despite extensive non-canonical editing of unknown functions, accurate canonical editing is required for normal cell growth. In PCF, REH2C controls editing fidelity in RESC-bound mRNAs. Here, we report that KREH2, a REH2C-associated helicase, developmentally controls programmed non-canonical editing, including an abundant 3' element in ATPase subunit 6 (A6) mRNA. The 3' element sequence is directed by a proposed novel regulatory gRNA. In PCF, KREH2 RNAi-knockdown up-regulates the 3' element, which establishes a stable structure hindering element removal by canonical initiator-gRNA-directed editing. In BSF, KREH2-knockdown does not up-regulate the 3' element but reduces its high abundance. Thus, KREH2 differentially controls extensive non-canonical editing and associated RNA structure via a novel regulatory gRNA, potentially hijacking factors as a 'molecular sponge'. Furthermore, this gRNA is bifunctional, serving in canonical CR4 mRNA editing whilst installing a structural element in A6 mRNA.

published proceedings

  • Nucleic Acids Res

altmetric score

  • 1.25

author list (cited authors)

  • Meehan, J., McDermott, S. M., Ivens, A., Goodall, Z., Chen, Z., Yu, Z., ... Cruz-Reyes, J.

citation count

  • 0

complete list of authors

  • Meehan, Joshua||McDermott, Suzanne M||Ivens, Alasdair||Goodall, Zachary||Chen, Zihao||Yu, Zihao||Woo, Jia||Rodshagen, Tyler||McCleskey, Laura||Sechrist, Rebecca||Stuart, Kenneth||Zeng, Lanying||Rouskin, Silvi||Savill, Nicholas J||Schnaufer, Achim||Zhang, Xiuren||Cruz-Reyes, Jorge

publication date

  • May 2023