Translational control of dosage compensation in Drosophila by Sex-lethal: cooperative silencing via the 5' and 3' UTRs of msl-2 mRNA is independent of the poly(A) tail

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Abstract
Translational repression of male‐specific‐lethal 2 (msl‐2) mRNA by Sex‐lethal (SXL) controls dosage compensation in Drosophila. In vivo regulation involves cooperativity between SXL‐binding sites in the 5′ and 3′ untranslated regions (UTRs). To investigate the mechanism of msl‐2 translational control, we have developed a novel cell‐free translation system from Drosophila embryos that recapitulates the critical features of mRNA translation in eukaryotes: cap and poly(A) tail dependence. Importantly, tight regulation of msl‐2 translation in this system requires cooperation between the SXL‐binding sites in both the 5′ and 3′ UTRs, as seen in vivo. However, in contrast to numerous other developmentally regulated mRNAs, the regulation of msl‐2 mRNA occurs by a poly(A) tail‐independent mechanism. The approach described here allows mechanistic analysis of translational control in early Drosophila development and has revealed insights into the regulation of dosage compensation by SXL.