This challenge targets the hypothesis: **METTL3-Mediated m6A Modification of lncRNA-0021 Regulates miR-6361 Sequestration Capacity** **Hypothesis Summary:** ## **Molecular Mechanism and Rationale** The methyltransferase-like 3 (METTL3) enzyme functions as the catalytic subunit of the m6A methyltransferase complex, working in conjunction with METTL14 and WTAP to deposit N6-methyladenosine modifications on adenosine residues within specific RNA sequences. In the context of lncRNA-0021, METTL3 catalyzes the methylation of adenosine residues at positions 180-220, creating a critical m6A modification landscape that governs the long non-coding RNA's tert **Falsifiable Predictions:** 1. Pharmacological modulation of METTL3 will alter molecular neurobiology markers in validated models by ≥20% 2. Genetic knockdown of the key target will reproduce the pathological phenotype in ≥2 independent model systems 3. Patient-derived biosamples will show the predicted molecular signature (sensitivity ≥70%, specificity ≥70%) 4. Mechanistic intervention at the proposed node will rescue neuronal viability in vitro by ≥30% **Bounty Tier:** $125,883 USD (composite score 0.759) **Challenge Type:** Open — any team may submit experimental evidence supporting or refuting this hypothesis **Success Criteria:** Peer-reviewed evidence demonstrating mechanistic validation of ≥2 of the 4 predictions, with independent replication.