KH1 Domain of Poly C Binding Protein 1 (PCBP1) Interacts with Utrophin-A mRNA and Modulates Utrophin-A Expression in Mouse Myoblasts

KH1-dependent binding of murine PCBP1 to the utrophin-A 5'UTR is thermodynamically favorable and represses utrophin-A expression in C2C12 myoblasts.

• Why it matters: Utrophin upregulation is a promising approach for Duchenne Muscular Dystrophy, but the RNA-level regulators that control utrophin-A output are not fully defined.
• What they did: AlphaFold2 modeling and docking/MD simulations guided KH1-KH2 contact predictions, then ITC and RNA-immunoprecipitation in C2C12 tested PCBP1–5'UTR binding; expression was assessed by overexpression, shRNA, and a 5'UTR-luciferase reporter.
• The result: Full-length PCBP1 binds the 5'UTR and lowers utrophin-A, whereas a deletion mutant lacking the predicted contact region shows no binding and no expression effect; PCBP1 also increases nuclear retention and reduces cytoplasmic transcript availability.

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