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Structural basis of gRNA stabilization and mRNA recognition in trypanosomal RNA editing.
Liu, Shiheng; Wang, Hong; Li, Xiaorun; Zhang, Fan; Lee, Jane K J; 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; Zhou, Z Hong.
Affiliation
  • Liu S; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA, USA.
  • Wang H; California NanoSystems Institute, University of California, Los Angeles, CA, USA.
  • Li X; Department of Molecular and Cell Biology, Boston University Medical Campus, Boston, MA, USA.
  • Zhang F; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA, USA.
  • Lee JKJ; California NanoSystems Institute, University of California, Los Angeles, CA, USA.
  • Li Z; School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
  • Yu C; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA, USA.
  • Hu JJ; California NanoSystems Institute, University of California, Los Angeles, CA, USA.
  • Zhao X; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA, USA.
  • Suematsu T; California NanoSystems Institute, University of California, Los Angeles, CA, USA.
  • Alvarez-Cabrera AL; Department of Physiology and Biophysics, University of California, Irvine, CA, USA.
  • Liu Q; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA, USA.
  • Zhang L; California NanoSystems Institute, University of California, Los Angeles, CA, USA.
  • Huang L; School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
  • Aphasizheva I; Department of Molecular and Cell Biology, Boston University Medical Campus, Boston, MA, USA.
  • Aphasizhev R; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA, USA.
  • Zhou ZH; California NanoSystems Institute, University of California, Los Angeles, CA, USA.
Science ; 381(6653): eadg4725, 2023 07 07.
Article in En | MEDLINE | ID: mdl-37410820
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Trypanosoma brucei brucei / RNA, Messenger / RNA, Protozoan / RNA, Guide, Kinetoplastida / RNA Editing / RNA Stability Language: En Journal: Science Year: 2023 Document type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Trypanosoma brucei brucei / RNA, Messenger / RNA, Protozoan / RNA, Guide, Kinetoplastida / RNA Editing / RNA Stability Language: En Journal: Science Year: 2023 Document type: Article