ID: h-e27562cbb4
Hypothesis
A-to-I RNA editing modulates the lncRNA-0021 binding site and tunes mmu-miR-6361 selectivity
ADAR-dependent editing could strengthen or weaken a pre-existing miR-6361 site by altering local pairing potential or RNA structure.
molecular neurobiology
EvidencePending (0%)📖 0 cit🗣 1 debates✓ 3 support✗ 2 oppose
✓ All Quality Gates Passed
🧪 Overview
ADAR-dependent editing could strengthen or weaken a pre-existing miR-6361 site by altering local pairing potential or RNA structure. The debate supports this as a plausible modifier of interaction strength, but not as the primary determinant of baseline specificity unless editing at the relevant adenosines is directly demonstrated.
🧬 Mechanism
🧬 Curated Mechanism Pathway
Curated pathway from expert analysis
flowchart TD
A["ADAR1/ADAR2<br/>Hypothesis Target"]
B["Pathway Dysregulation<br/>Cited Mechanism"]
C["Cellular Response<br/>Stress or Clearance Change"]
D["Neural Circuit Effect<br/>Synapse/Glia Vulnerability"]
E["AD<br/>Disease-Relevant Outcome"]
A --> B
B --> C
C --> D
D --> E
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style B fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style E fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a⚖️ Evidence
⚖️ Evidence Matrix3 supports2 contradicts
Contradicts
There is no direct evidence that lncRNA-0021 is edited at the relevant site, and most such interactions do not require editing to exist.
Contradicts
As framed, editing could either enhance or impair binding, making it a weak primary hypothesis unless narrowed to a specific edited nucleotide.
📖 Linked Papers
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — ADAR1
No curated PDB or AlphaFold mapping for ADAR1 yet. Search RCSB →
💉 Clinical Trials
No clinical trials data linked to this hypothesis yet.
No curated ClinVar variants loaded for this hypothesis.
Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.
No DepMap CRISPR Chronos data found for ADAR1.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
💰 Estimated Development
Cost
$0
Timeline
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🏆 Tournament
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📊 Market Indicators
7d Trend
↗
Rising
7d Momentum
▲ 1.1%
Volatility
Medium
0.0202
Events (7d)
3
Price History
▲21.7%💾 Resource Usage
LLM Tokens
11,368
$0.0341
Total Cost
$0.0341
🔮 Predictions
🔎 Predictions vs Observations2 predictions · 0 with recorded observations
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF ADAR1 and ADAR2 are simultaneously knocked down using siRNA in primary mouse cortical neurons, THEN the expression of a miR-6361 target reporter construct will increase by at least 2-fold relative | At least 2-fold upregulation of luciferase activity from a reporter containing the miR-6361 binding site from lncRNA-0021, indicating reduced competition for mi | — no observation — | pending | 0.55 |
| IF the A-to-I editing site at position 247 of lncRNA-0021 is reverted to unmodified adenosine (A247) via site-directed mutagenesis in N2A cells, THEN mmu-miR-6361 binding affinity will decrease by at | Decreased miR-6361 binding affinity (≥30% reduction) to the unedited lncRNA-0021 A247 variant relative to the edited construct, as measured by RNA immunoprecipi | — no observation — | pending | 0.65 |
🔮 Falsifiable Predictions (2)
pendingconf 65%
IF the A-to-I editing site at position 247 of lncRNA-0021 is reverted to unmodified adenosine (A247) via site-directed mutagenesis in N2A cells, THEN mmu-miR-6361 binding affinity will decrease by at least 30% compared to the edited variant within 72 hours post-transfection.
Predicted outcome: Decreased miR-6361 binding affinity (≥30% reduction) to the unedited lncRNA-0021 A247 variant relative to the edited construct, as measured by RNA imm
Falsification: No significant difference (<10% change) in miR-6361 binding affinity between the edited (I247) and unedited (A247) lncRNA-0021 variants would disprove this prediction and indicate editing is not a pri
pendingconf 55%
IF ADAR1 and ADAR2 are simultaneously knocked down using siRNA in primary mouse cortical neurons, THEN the expression of a miR-6361 target reporter construct will increase by at least 2-fold relative to scrambled siRNA controls within 96 hours post-transfection.
Predicted outcome: At least 2-fold upregulation of luciferase activity from a reporter containing the miR-6361 binding site from lncRNA-0021, indicating reduced competit
Falsification: No significant change (<1.2-fold) in reporter activity following ADAR1/2 double knockdown would disprove this prediction and indicate that ADAR-mediated editing does not modulate miR-6361 bioavailabil
▸Metadatasource: v1_phase_c_backfill · origin_type: debate_synthesizer
| source | v1_phase_c_backfill |
| origin_type | debate_synthesizer |
| _schema_version | 1 |
📊 Evidence Profile
Evidence Balance
+0%
Certainty
0%
Debates
0
Incoming
0
Outgoing
0
0 supporting
0 contradicting
0 neutral
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