CELF1 regulates lens development through direct repression of target mRNAs

Disruption of the gene encoding the RNA-binding protein CELF1 leads to early-onset cataract in mice. Here, using iCLIP-seq in lenses, we mapped transcriptome-wide CELF1 binding sites, revealing interactions with the 3′UTRs of key transcripts involved in lens development and pathology, including Pax6, Prox1, Jag1, Maf, and Gja8.

Integration with transcriptomic data and luciferase reporter assays demonstrated that CELF1 binding represses its target mRNAs by destabilizing transcripts and/or inhibiting their translation. Consistently, Maf and Gja8 are upregulated in Celf1-cKO lenses. In Xenopus laevis, forced overexpression of maf disrupted lens structure and eye morphology, confirming the developmental relevance of CELF1-mediated repression.