The most likely explanation is a two-factor recognition mechanism: a canonical miRNA seed-complementary site in lncRNA-0021 provides initial specificity, while a favorable local secondary structure or central pairing pattern raises affinity enough to distinguish mmu-miR-6361 from other seed-sharing candidates. This explains why seed complementarity is necessary but not by itself sufficient for selective binding.
Curated pathway from expert analysis
flowchart TD
A["lncRNA-0021<br/>Hypothesis Target"]
B["Complement<br/>Cited Mechanism"]
C["Cellular Response<br/>Stress or Clearance Change"]
D["Neural Circuit Effect<br/>Synapse/Glia Vulnerability"]
E["Neurodegeneration<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:#ef9a9aNo linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for LNCRNA-0021 yet. Search RCSB →
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.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF the local secondary structure surrounding the seed site in lncRNA-0021 is disrupted by synonymous mutations that maintain the seed complementarity while reducing base-pairing stability (ΔG > -5 kca | Selectivity ratio for mmu-miR-6361 vs. seed-sharing miRNAs drops from >10-fold to <2-fold with structure-disrupted mutant | — no observation — | pending | 0.70 |
| IF the seed-complementary site in lncRNA-0021 is mutated to abolish complementarity with mmu-miR-6361 (while preserving the local secondary structure), THEN binding affinity for mmu-miR-6361 will decr | Binding affinity decreases >80% (Kd increases >5-fold) for mmu-miR-6361 with seed-site mutant lncRNA-0021 | — no observation — | pending | 0.75 |