Promiscuity in post-transcriptional control of gene expression: Drosophila sex-lethal and its regulatory partnerships

The Drosophila RNA-binding protein Sex-lethal (Sxl) is a potent post-transcriptional regulator of gene expression that controls female development. It regulates the expression of key factors involved in sex-specific differences in morphology, behavior, and dosage compensation. Functional Sxl protein is only expressed in female flies, where it binds to U-rich RNA motifs present in its target mRNAs to regulate their fate. Sxl is a very versatile regulator that, by shuttling between the nucleus and the cytoplasm, can regulate almost all aspects of post-transcriptional gene expression including RNA processing, nuclear export, and translation. For these functions, Sxl employs multiple interactions to either antagonize RNA-processing factors or to recruit various coregulators, thus allowing it to establish a female-specific gene expression pattern. Here, we summarize the current knowledge about Sxl function and review recent mechanistic and structural studies that further our understanding of how such a seemingly 'simple' RNA-binding protein can exert this plethora of different functions.