RNA-binding protein RBM34 promotes hepatic fibrosis by enhancing DROSHA-mediated nuclear export of Loxl2 mRNA.

RBM34 is markedly upregulated in human and murine fibrotic livers, where it enhances DROSHA-mediated nuclear export and translation of Loxl2 mRNA in activated hepatic stellate cells.

• Why it matters: Hepatic fibrosis depends on activated hepatic stellate cells depositing excessive ECM, but how RNA-binding proteins regulate this activation is not well defined, leaving RBM34’s role unclear.
• What they did: The study used STAMP and RNA immunoprecipitation to identify Loxl2 mRNA as a direct RBM34 target, then showed RBM34 interacts with DROSHA to promote nuclear export and translation independently of DROSHA’s canonical RNase III activity.
• The result: RBM34 boosted fibrotic marker expression and HSC contractility, and HSC-specific knockdown attenuated liver fibrosis in vivo, supporting the RBM34–DROSHA–LOXL2 axis as a driver and therapeutic target.

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