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| Title | Structural basis for guide RNA selection by the RESC1-RESC2 complex. |
|---|---|
| Journal, issue, pages | Nucleic Acids Res, Vol. 51, Issue 9, Page 4602-4612, Year 2023 |
| Publish date | Mar 31, 2023 |
 Authors | Luciano G Dolce / Yevheniia Nesterenko / Leon Walther / Félix Weis / Eva Kowalinski /   |
| PubMed Abstract | Kinetoplastid parasites, such as trypanosomes or leishmania, rely on RNA-templated RNA editing to mature mitochondrial cryptic pre-mRNAs into functional protein-coding transcripts. Processive pan- ...Kinetoplastid parasites, such as trypanosomes or leishmania, rely on RNA-templated RNA editing to mature mitochondrial cryptic pre-mRNAs into functional protein-coding transcripts. Processive pan-editing of multiple editing blocks within a single transcript is dependent on the 20-subunit RNA editing substrate binding complex (RESC) that serves as a platform to orchestrate the interactions between pre-mRNA, guide RNAs (gRNAs), the catalytic RNA editing complex (RECC), and a set of RNA helicases. Due to the lack of molecular structures and biochemical studies with purified components, neither the spacio-temporal interplay of these factors nor the selection mechanism for the different RNA components is understood. Here we report the cryo-EM structure of Trypanosoma brucei RESC1-RESC2, a central hub module of the RESC complex. The structure reveals that RESC1 and RESC2 form an obligatory domain-swapped dimer. Although the tertiary structures of both subunits closely resemble each other, only RESC2 selectively binds 5'-triphosphate-nucleosides, a defining characteristic of gRNAs. We therefore propose RESC2 as the protective 5'-end binding site for gRNAs within the RESC complex. Overall, our structure provides a starting point for the study of the assembly and function of larger RNA-bound kinetoplast RNA editing modules and might aid in the design of anti-parasite drugs. |
 External links | Nucleic Acids Res / PubMed:36999600 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 3.4 - 4.7 Å |
| Structure data | EMDB-16592, PDB-8cdp:  EMDB-16593: Cryo-EM map of RESC1-RESC2 bound to gRNA |
| Source |
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 Keywords |  RNA BINDING PROTEIN / RESC / RNA editing / cryo-EM structure / Trypanosoma brucei |
