ID: h-49112ee4c0
Hypothesis
A pre-organized hairpin or loop in lncRNA-0021 creates a high-affinity docking surface for mmu-miR-6361
lncRNA-0021 may contain a pre-folded structural element that lowers the entropic cost of binding and presents the miR-6361-complementary nucleotides in an accessible geometry.
molecular neurobiology
EvidencePending (0%)📖 0 cit🗣 1 debates✓ 3 support✗ 2 oppose
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🧪 Overview
lncRNA-0021 may contain a pre-folded structural element that lowers the entropic cost of binding and presents the miR-6361-complementary nucleotides in an accessible geometry. In this model, selectivity arises from the combination of sequence complementarity and an RNA fold that non-cognate miRNAs cannot exploit efficiently.
🧬 Mechanism
🧬 Curated Mechanism Pathway
Curated pathway from expert analysis
flowchart TD
A["lncRNA-0021 Structured Hairpin<br/>Pre-organized Binding Surface"]
B["miR-6361 Seed Accessibility<br/>High-Affinity Docking Geometry"]
C["miR-6361 Sequestration<br/>Reduced Target Repression"]
D["Downstream Transcript Derepression<br/>Inflammatory or stress-effector output"]
E["RNA Structure-Function Liability<br/>Disease-relevant signaling shift"]
A --> B
B --> C
C --> D
D --> E
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style C fill:#7b1fa2,stroke:#ce93d8,color:#ce93d8
style E fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a⚖️ Evidence
⚖️ Evidence Matrix3 supports2 contradicts
Supports
Pre-existing structural elements in lncRNAs can facilitate specific small-RNA binding by reducing conformational penalties.
Supports
Exosomal lncRNAs often carry stabilized motifs compatible with persistence and structured recognition.
Contradicts
lncRNAs often occupy dynamic structural ensembles, so a single pre-formed docking structure may be an oversimplification.
Contradicts
Bulk structural assays such as SHAPE cannot by themselves distinguish pre-organization from induced fit after miRNA binding.
📖 Linked Papers
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — LNCRNA-0021
No curated PDB or AlphaFold mapping for LNCRNA-0021 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 lncRNA-0021.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
💰 Estimated Development
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🔮 Predictions
🔎 Predictions vs Observations2 predictions · 0 with recorded observations
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF we mutate nucleotides 23-42 of lncRNA-0021 (disrupting the predicted hairpin stem by converting GC pairs to GA mismatches while preserving the loop sequence), THEN the equilibrium binding constant | Kd increase from ~50 pM (predicted wild-type) to >250 pM for the miR-6361-lncRNA-0021 complex | — no observation — | pending | 0.65 |
| IF we measure binding affinities of lncRNA-0021 for a panel of 8 miRNAs (mmu-miR-6361 plus 7 non-cognate miRNAs with partial complementarity but different seed regions), THEN the cognate miR-6361 show | miR-6361 Kd <100 pM; all non-cognate miRNAs Kd >1 nM | — no observation — | pending | 0.60 |
🔮 Falsifiable Predictions (2)
pendingconf 65%
IF we mutate nucleotides 23-42 of lncRNA-0021 (disrupting the predicted hairpin stem by converting GC pairs to GA mismatches while preserving the loop sequence), THEN the equilibrium binding constant (Kd) for mmu-miR-6361 increases by at least 5-fold compared to wild-type within 4 weeks of measureme
Predicted outcome: Kd increase from ~50 pM (predicted wild-type) to >250 pM for the miR-6361-lncRNA-0021 complex
Falsification: Mutant lncRNA-0021 retains Kd within 2-fold of wild-type, indicating the predicted hairpin is not essential for high-affinity binding
pendingconf 60%
IF we measure binding affinities of lncRNA-0021 for a panel of 8 miRNAs (mmu-miR-6361 plus 7 non-cognate miRNAs with partial complementarity but different seed regions), THEN the cognate miR-6361 shows at least 10-fold higher affinity than all non-cognate miRNAs within 6 weeks of measurement.
Predicted outcome: miR-6361 Kd <100 pM; all non-cognate miRNAs Kd >1 nM
Falsification: Any non-cognate miRNA achieves Kd within 5-fold of miR-6361, indicating sequence complementarity alone (not structural selectivity) drives binding
▸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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