Absence of interdomain contacts in the crystal structure of the RNA recognition motifs of sex-lethal

By binding specific RNA transcripts, the Sex-lethal protein (SXL) governs s exual differentiation and dosage compensation in Drosophila melanogaster. T o investigate the basis for RNA binding specificity, we determined the crys tal structure of the tandem RNA recognition motifs (RRMs) of SXL. Both RRMs adopt the canonical RRM fold, and the 10-residue, interdomain linker shows significant disorder. In contrast to the previously determined structure o f the two-RRM fragment of heterogeneous nuclear ribonucleoprotein Al, SXL d isplays no interdomain contacts between RRMs. These results suggest that th e SXL RRMs are flexibly tethered in solution, and RNA binding restricts the orientation of RRMs. Therefore, the observed specificity for single-strand ed, U-rich sequences does not arise from a predefined, rigid architecture o f the isolated SXL RRMs.