Structural basis of the RNA-editing cascade in trypanosome mitochondria.
The molecular mechanism of uridine insertion-and-deletion mRNA editing in trypanosome mitochondria 1-4 has remained unclear because of the highly dynamic nature of the underlying multi-enzyme machinery 5 . Here, we define editosomes as supramolecular assemblies formed by the RNA-editing substrate-binding complex (RESC) and either RNA-editing catalytic complex 1 or 2 (RECC1 or RECC2) 6 , and present cryo-electron microscopy structures of the approximately 1-MDa RECC1 and RECC2. Resembling dragonf
The molecular mechanism of uridine insertion-and-deletion mRNA editing in trypanosome mitochondria 1-4 has remained unclear because of the highly dynamic nature of the underlying multi-enzyme machinery 5 . Here, we define editosomes as supramolecular assemblies formed by the RNA-editing substrate-binding complex (RESC) and either RNA-editing catalytic complex 1 or 2 (RECC1 or RECC2) 6 , and present cryo-electron microscopy structures of the approximately 1-MDa RECC1 and RECC2. Resembling dragonflies, with a head, thorax-like core, tail and wings, these ribonucleoproteins mediate the uridine deletion and uridine insertion cascades, respectively. In each RECC, a tetrameric core containing one active and three inactive RNase III domains captures the guide RNA (gRNA)-mRNA duplex, while auxiliary zinc fingers distinguish deletion sites from insertion sites and position the substrate for mRNA cleavage (step I). Three peripheral oligonucleotide-binding-fold heterotetramers are flexibly attached to the core, forming a spatially adaptable reaction chamber. The tail recruits the exonuclease and uridylyltransferase that remove or add uridines (step II), whereas the wings, coordinated by an architectural tRNA, position RNA ligases to seal the edited mRNA (step III). Together, these structures reveal how gRNA-directed substrate recognition, mRNA cleavage, uridine deletion and insertion and ligation are integrated in a single macromolecular machine. This architecture defines the mechanism of information transfer in RNA editing.
