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TitleStructural basis of gRNA stabilization and mRNA recognition in trypanosomal RNA editing.
Journal, issue, pagesScience, Vol. 381, Issue 6653, Page eadg4725, Year 2023
Publish dateJul 7, 2023
AuthorsShiheng Liu / Hong Wang / Xiaorun Li / Fan Zhang / Jane K J Lee / Zihang Li / Clinton Yu / Jason J Hu / Xiaojing Zhao / Takuma Suematsu / Ana L Alvarez-Cabrera / Qiushi Liu / Liye Zhang / Lan Huang / Inna Aphasizheva / Ruslan Aphasizhev / Z Hong Zhou /
PubMed AbstractIn , the editosome, composed of RNA-editing substrate-binding complex (RESC) and RNA-editing catalytic complex (RECC), orchestrates guide RNA (gRNA)-programmed editing to recode cryptic mitochondrial ...In , the editosome, composed of RNA-editing substrate-binding complex (RESC) and RNA-editing catalytic complex (RECC), orchestrates guide RNA (gRNA)-programmed editing to recode cryptic mitochondrial transcripts into messenger RNAs (mRNAs). The mechanism of information transfer from gRNA to mRNA is unclear owing to a lack of high-resolution structures for these complexes. With cryo-electron microscopy and functional studies, we have captured gRNA-stabilizing RESC-A and gRNA-mRNA-binding RESC-B and RESC-C particles. RESC-A sequesters gRNA termini, thus promoting hairpin formation and blocking mRNA access. The conversion of RESC-A into RESC-B or -C unfolds gRNA and allows mRNA selection. The ensuing gRNA-mRNA duplex protrudes from RESC-B, likely exposing editing sites to RECC-catalyzed cleavage, uridine insertion or deletion, and ligation. Our work reveals a remodeling event facilitating gRNA-mRNA hybridization and assembly of a macromolecular substrate for the editosome's catalytic modality.
External linksScience / PubMed:37410820 / PubMed Central
MethodsEM (single particle)
Resolution3.3 - 3.7 Å
Structure data

EMDB-29305, PDB-8fn4:
Cryo-EM structure of RNase-treated RESC-A in trypanosomal RNA editing
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-29306, PDB-8fn6:
Cryo-EM structure of RNase-untreated RESC-A in trypanosomal RNA editing
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-29308, PDB-8fnc:
Cryo-EM structure of RNase-treated RESC-C in trypanosomal RNA editing
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-29311, PDB-8fnf:
Cryo-EM structure of RNase-untreated RESC-C in trypanosomal RNA editing
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-29314, PDB-8fni:
Cryo-EM structure of RNase-treated RESC-B in trypanosomal RNA editing
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-29316, PDB-8fnk:
Cryo-EM structure of RNase-untreated RESC-B in trypanosomal RNA editing
Method: EM (single particle) / Resolution: 3.7 Å

Chemicals

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM / Adenosine triphosphate

Source
  • trypanosoma brucei (eukaryote)
KeywordsRNA BINDING PROTEIN/RNA / HEAT repeat / trypanosoma / RNA editing substrate binding complex / gRNA / RNA BINDING PROTEIN-RNA complex

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