The Masc-PSI complex directly induces male-type doublesex splicing in silkworms

The WZ sex determination system is found in a diverse range of animals, including lepidopteran insects. In the silkworm Bombyx mori, the masculinizing protein Masculinizer (BmMasc) induces the production of the male-type Bombyx mori doublesex (Bmdsx^M), which is the master genetic switch of B. mori sex differentiation. However, the molecular mechanism through which BmMasc transduces the masculinizing signal to the Bmdsx^M production remains unknown. Here, we show that BmMasc physically interacts with Bombyx mori P-element somatic inhibitor (BmPSI), a RNA binding protein required for Bmdsx^M expression. Knockdown experiments indicate that BmPSI is essential for the masculinizing activity of BmMasc. RNA immunoprecipitation experiments also reveal that BmMasc-containing protein complex is associated with female-specific regions of Bmdsx pre-mRNA. Taken together, our findings show that the BmMasc-BmPSI protein complex binds to female-specific Bmdsx regions, inducing exon skipping, and thereby promoting Bmdsx^M expression in B. mori males.