1. Structural basis of gRNA stabilization and mRNA recognition in trypanosomal RNA editing
- Author
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Liu, Shiheng, Wang, Hong, Li, Xiaorun, Zhang, Fan, Lee, Jane KJ, Li, Zihang, Yu, Clinton, Hu, Jason J, Zhao, Xiaojing, Suematsu, Takuma, Alvarez-Cabrera, Ana L, Liu, Qiushi, Zhang, Liye, Huang, Lan, Aphasizheva, Inna, Aphasizhev, Ruslan, and Zhou, Z Hong
- Subjects
Biochemistry and Cell Biology ,Chemical Sciences ,Biological Sciences ,Genetics ,Vector-Borne Diseases ,Generic health relevance ,Good Health and Well Being ,Cryoelectron Microscopy ,Protozoan Proteins ,RNA Editing ,RNA ,Guide ,Kinetoplastida ,RNA ,Messenger ,Trypanosoma brucei brucei ,RNA Stability ,RNA ,Protozoan ,General Science & Technology - Abstract
In Trypanosoma brucei, 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.
- Published
- 2023