Abstract
In vertebrates, two genes, Musashi1 (Msi1) and Musashi2 (Msi2), encode for highly similar Musashi protein paralogs. The Musashi proteins are known to bind to 3'-UTRs and control translation. In photoreceptor cells, the Musashi proteins promote the inclusion of photoreceptor-specific alternative exons by binding to the proximal downstream of their introns. While the Musashi proteins are expressed in various cell types, their role in regulating splicing appears to be confined to photoreceptor cells, where the two proteins have exceptionally high expression levels. To test if the photoreceptor-specific role of MSI1 and MSI2 in splicing is due to their expression levels in photoreceptor cells, we generated combined Msi1 and Msi2 knockouts that progressively reduced the number of Musashi alleles in photoreceptor cells. We analyzed the splicing of photoreceptor-specific exons in the Cc2d2a, Cep290, Prom1, and Ttc8 genes and the function of photoreceptor cells in the knockouts. We found that a single allele from either Msi1 or Msi2 is sufficient to maintain photoreceptor function and support high inclusion levels of the photoreceptor-specific exons.