Sun et al. 2026 — RBM24 alternative splicing is essential for cochlear hair cell stereocilia integrity
Citation: Chunjiao Sun, Jingshuang Zhao, Nana Li, Xuebo Yao, Yanfei Wang, Chul Hoon Kim, Jinwoong Bok, Anthony W Peng, Zhigang Xu. “Alternative splicing of the Rbm24 gene is essential for cochlear hair cell stereocilia integrity and hearing function in mice.” PNAS 123:e2531564123, 2026. PMID 41973913. DOI 10.1073/pnas.2531564123.
Source note: Supersedes/extends sources/2026-04-17-sun-rbm24-strc-splicing.md (created 2026-04-17). Raw source note preserved; this formal paper note contains the verified citation and the dose-response gap documentation.
Full text access: PNAS 403 error on direct fetch (2026-04-25). PubMed abstract confirmed. Anna’s Archive not indexed. Abstract sufficient to confirm core finding and dose-response absence.
Numbers that matter (or notably absent)
| Parameter | Reported? | Value / Status |
|---|---|---|
| RBM24 isoforms generated by exon 4 splicing | Yes | 2 isoforms: RBM24-L (with exon 4) and RBM24-S (without) |
| Functional isoform required in OHC | Yes | RBM24-L (exon 4-containing) |
| STRC as RBM24 target | Yes | ”Strc is identified as a dysregulated RBM24 target” |
| RBM24 dose-response curve (K_M, Hill n) | NO | Not published |
| RBM24 protein titration vs STRC mRNA output | NO | Not published |
| Hill coefficient for RBM24→STRC splicing | NO | NOT MEASURED in this paper |
| Quantitative fold-change STRC mRNA with/without RBM24 | Not in abstract | Not confirmed in accessible text |
| Overexpression phenotype | Yes | RBM24-L overexpression causes hearing loss and stereocilia disorganization (similar to deletion) |
Core finding
RBM24 produces two isoforms via alternative splicing. Exon 4 inclusion generates RBM24-L, the functionally required form in OHCs. Exon 4 deletion causes stereocilia disorganization, progressive OHC loss, and hearing loss confirmed by ABR/DPOAE. Overexpression of RBM24-L causes similar damage — suggesting tight stoichiometric control is required. STRC is identified as a direct RBM24 splicing target.
Critical gap for h06 modeling
This paper does NOT provide:
- A dose-response curve for RBM24 protein level vs STRC mRNA splicing output
- Any K_M or Hill coefficient values
- Any quantitative titration of the RBM24→STRC regulatory axis
The Hill coupling constants (HILL_K = 200, HILL_N = 2, MAX_BOOST = 3) in mrna_lnp_pkpd_integration*.py cannot be derived from this paper. They remain CIRCULAR ODE FITS with no primary-literature backing.
The qualitative finding that “RBM24-L overexpression causes similar damage as deletion” actually suggests the dose-response relationship is non-monotonic (bell-shaped) rather than a simple Hill saturation — which further invalidates the Hill model’s unidirectional assumption.
WARNING: no primary measurement of RBM24→STRC dose-response in OHCs. Hill K_M, n, max_boost are scenario-scan parameters only. See mrna_lnp_pkpd_integration*.py.
Connections
[supersedes]sources/2026-04-17-sun-rbm24-strc-splicing— upgraded to formal paper note[source]STRC h06 Parameter Provenance Audit 2026-04-23[source]STRC h06 Parameter Provenance Audit 2026-04-25[supports]STRC RBM24 Regulatory Hypothesis — confirms STRC as direct RBM24 target[applies]STRC mRNA Therapy Hypothesis[see-also]STRC h06 Hill Sensitivity Sweep 2026-04-23