ADAR_LICENSING

Scope

ADAR1 p150 licensing during antiviral stress and viral infection, especially links among RNAi/RISC, DROSHA/DGCR8-associated RNA processing, SeV 5T/5R controls, and interferon induction.

Current Working Model

ADAR1 p150 substrate selection/editing is licensed or shaped by AGO2/RISC and DROSHA-associated RNA-processing machinery during infection. Simple local RNA structure, simple bowtie motifs, and Drosha-as-ADAR-competitor models are superseded or rejected in the current reconstruction. siDROSHA should be treated as reducing editing in ADAR-competent settings unless new data supersede that.

People

• Morgane Baldaccini: lead postdoc; RNA biology/biochemistry.
• Ryla Cantorgenali: related microRNA gate work.
• Cross-links to VECTOR DELIVERY and SeV 5T/5R systems.

Known Analyses / Artifacts

• ADAR_IFN_RISC_DROSHA_SeV5T_Reconstruction_20260704.md
• RNAfold/ViennaRNA analyses comparing DROSHA-dependent and DROSHA-independent ADAR1 editing sites.
• 50+50 RNAfold report: results/rnafold_drosha_dependent_adar_structures_50x50/RNAfold_DROSHA_ADAR_structure_report_50x50.md
• Summary PDF: rnafold_ADAR_DROSHA_structure_summary_figures_50x50.pdf
• Prior 25+25 representative-set analysis.

Open Questions

• Exact biochemical mechanism by which AGO2/RISC and DROSHA/DGCR8 influence ADAR1 substrate selection.
• Whether additional RNA-binding proteins license ADAR1 in infection contexts.
• Final figure/manuscript spine and main-versus-supplement organization.

TODO

• Import full ADAR primer, encyclopedia, methods, datasets, figures, legacy, and changelog files if available.

v0.5 Conceptual Reframing

This project should be treated as an example of an engineered-system failure revealing fundamental biology.

The starting observation was that miRNA-based silencing can be thwarted by ADAR1-mediated editing of target sequences, allowing silencing to be stopped or escaped. Morgane's work expanded this into a broader model in which infection changes the role of RNAi-associated biology. Rather than acting primarily as a canonical antiviral RNAi system, vertebrate RNAi machinery may have been repurposed as a licensing layer for ADAR1.

v0.5 Working Hypothesis

During infection, RNAi-associated machinery may help license ADAR1 to dissolve, edit, or resolve RNA substrates, potentially helping distinguish PAMP-like RNA from host RNA.

This evolutionary interpretation should remain explicitly labeled as a hypothesis until directly supported.

Programmatic Connection

Together with IMMUNE HIERARCHY, this project illustrates a broader lab theme: mature engineering tools can expose unexpected host biology. The novelty of the project should not be framed as miRNA silencing itself, but as the biological model revealed by the failure mode.