Structural basis of gRNA stabilization and mRNA recognition in trypanosomal RNA editing

• DOI: 10.1126/science.adg4725
• Publication Date: 2023-07-06T17:59:21Z
• Authors: Shiheng 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-Ca...; Qiushi Liu; Liye Zhang; Lan Huang; Inna Aphasizheva; Ruslan Aphasizhev; Z. Hong Zhou
• Keywords: Guide RNA

In Trypanosoma brucei, the editosome, composed of RNA-editing substrate-binding complex (RESC) and catalytic (RECC), orchestrates guide RNA (gRNA)-programmed editing to recode cryptic mitochondrial transcripts into messenger RNAs (mRNAs). The mechanism information transfer from gRNA mRNA is unclear owing a lack high-resolution structures for these complexes. With cryo-electron microscopy functional studies, we have captured gRNA-stabilizing RESC-A gRNA-mRNA-binding RESC-B RESC-C particles. sequesters termini, thus promoting hairpin formation blocking access. conversion or -C unfolds allows selection. ensuing gRNA-mRNA duplex protrudes RESC-B, likely exposing sites RECC-catalyzed cleavage, uridine insertion deletion, ligation. Our work reveals remodeling event facilitating hybridization assembly macromolecular substrate editosome's modality.