The translationally regulated msl-2 mRNP from Drosophila

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Dosage compensation in Drosophila melanogaster requires the male-specific expression of the MSL (male-specific lethal) complex. The male-specific expression of the MSL-2 subunit of this complex represents the key difference in the dosage compensation pathway. MSL-2 protein expression is inhibited posttranscriptionally in females by the female-specific RNA binding protein Sex-Lethal (SXL), which inhibits ms1-2 expression by an integrated two step mechanism via SXL binding sites in both the 5' UTR and the 3' UTR of the ms1-2 pre mRNA. SXL binding to the 5' UTR sites enforces the retention of the intron which is removed in male flies. Following export of this mRNA into the cytoplasm, SXL bound to these retained 5' UTR sites synergizes with additional SXL bound to the 3' UTR sites to establish a translational repressed ms1-2 mRNA-protein complex (mRNP). We have recapitulated the translational regulation in a cell-free system from Drosophila embryos using in vitro transcribed mRNAs and recombinant SXL protein. We propose to dissect the silenced mRNP by biochemical analysis of functionally important cis-acting elements, the functional domains of the trans-acting factor SXL and the identification of co-factors.