Conformational reorganization and phase separation drive hyper-editing of ADR-2–ADBP-1 complex
Adenosine deaminase acting on RNA (ADAR) proteins, which mediate adenosine-to-inosine editing of double-stranded ribonucleic acid (dsRNA) substrates, play essential roles in balancing innate immunity. Using cryogenic electron microscopy, we solved the structure of the Caenorhabditis elegans ADR-2-ADBP-1 complex (stoichiometric ratio, 2:2), which is an asymmetric ADR-2 dimer with one editing site blocked by the other ADR-2. Unexpectedly, dsRNA recruitment triggered dissociation of the ADR-2 dimer, exposing more competent dsRNA editing sites. Furthermore, high dsRNA and protein concentrations caused the formation of liquid-liquid phase-separated puncta, in which significantly greater editing activity was observed, indicating that organizational transitions enable the ADR-2-ADBP-1 complex to perform dsRNA hyper-editing. Our findings suggest that the ADAR editing mechanism adapts to different conditions via conformational reorganization.
Authors
- Zhen Zhang (ORCID: https://orcid.org/0000-0002-7444-6692)
- Chenyang Xue (ORCID: https://orcid.org/0000-0002-9603-3426)
- Jianqiang Mu
- Zi Wang (ORCID: https://orcid.org/0000-0001-5217-3948)
- Cang Wu (ORCID: https://orcid.org/0000-0002-6218-8569)
- Kaiming Xu (ORCID: https://orcid.org/0009-0006-4797-4592)
- Jingwei Yu (ORCID: https://orcid.org/0000-0003-4268-436X)
- Zhongmin Liu (ORCID: https://orcid.org/0000-0002-3280-3890)
- Xinmeng Chen (ORCID: https://orcid.org/0000-0002-8076-1517)
- Guangshuo Ou (ORCID: https://orcid.org/0000-0003-1512-7824)
- Xingang Liu (ORCID: https://orcid.org/0000-0003-2258-4265)
- Yanhong Chen (ORCID: https://orcid.org/0000-0003-2175-3936)
- Yajuan Fu (ORCID: https://orcid.org/0000-0001-6224-8579)
Institutions
- King Center (US)
- Southern University of Science and Technology (CN)
- Center for Life Sciences (CN)
- Tsinghua University (CN)
Publication Details
- Journal
- Nucleic Acids Research
- Published
- 2025-02-27
- DOI
- https://doi.org/10.1093/nar/gkaf148
- Citations
- 1
- Primary Topic
- RNA regulation and disease
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- National Natural Science Foundation of China
- Southern University of Science and Technology
- Guangdong Province Introduction of Innovative R&D Team
- Guangdong Provincial Pearl River Talents Program
- Basic and Applied Basic Research Foundation of Guangdong Province