STRC RBM24 Exon Splicing Quantification
Sun et al. 2026 SD03 dataset (rMATS SE analysis, Rbm24-exon4-KO vs control cochlea) contains 4 significant exon-skipping events in Strc. Two are in-frame and therapeutically relevant.
In-frame events (biologically interpretable)
| Event | mm10 coords (chr2 −) | Size | dPSI | FDR |
|---|---|---|---|---|
| E1 | 121203399–121203567 | 168 nt = 56 aa | −0.542 | 2.1 × 10⁻⁵ |
| E2 | 121198816–121198894 | 78 nt = 26 aa | −0.437 | 3.7 × 10⁻³ |
Divisibility test: 168 ÷ 3 = 56.0 ✓ | 78 ÷ 3 = 26.0 ✓
Frameshift events (not interpretable as natural isoforms)
| Event | Size | ÷3 |
|---|---|---|
| E3 | 70 nt | 23.33 ❌ |
| E4 | 197 nt | 65.67 ❌ |
Key finding
When RBM24 is absent, STRC exon inclusion drops 44–54% at two in-frame sites. This is consistent with RBM24 acting as a splicing enhancer for these exons — without it, the spliceosome skips them at high frequency.
Resolved (2026-04-20) — human protein mapping
Cross-species aa mapping via Ensembl canonical transcripts + BLOSUM62 alignment. All 4 events fall inside mini-STRC (aa 700–1775). TMEM145 interface empirically extracted from AF3 Job 2 CIF: aa 1603–1770 (C-terminal ARM repeats, not 950–1200 as earlier estimated). Full mapping in STRC RBM24 Exon Mapping to Human Protein.
| Event | Human aa | In mini-STRC | Distance to TMEM145 interface |
|---|---|---|---|
| E1 | 1047–1102 | ✅ | 501 aa upstream |
| E2 | 1311–1376 | ✅ | 227 aa upstream |
| E3 | 712–732 | ✅ (boundary) | 871 aa upstream |
| E4 | 1311–1376 | ✅ | 227 aa upstream |
None of the events directly overlap the TMEM145 interface. E1 (56 aa) is extremely conserved across mammals (100 % in chimp, 98 % rabbit, 93–95 % rodent/dog/pig), so it is functionally important — but not via TMEM145. E3 and E4 are frameshift events that trigger NMD.
Connections
[source]2026-04-17-sun-rbm24-strc-splicing — data origin[part-of]STRC RBM24 Regulatory Hypothesis — experimental evidence for this hypothesis[supports]STRC Mini-STRC Single-Vector Hypothesis — confirmed: all 4 regulated exons fall in therapeutic window- STRC RBM24 Exon Mapping to Human Protein — human aa positions for each event
[see-also]STRC mRNA Therapy Hypothesis — alternative delivery strategy that bypasses splicing[about]Jeffrey Holt — Sun et al. editor; Derstroff et al. co-author