To gain further insight into translation control mechanisms we are studying as a model system the Drosophila RNA-binding protein Sex Lethal (Sxl). Sxl is an important post-transcriptional regulator in female flies with diverse functions in several aspects of RNA biology ranging from the regulation of splicing and poly-A site choice to the control of translation.

Its translation regulatory properties were characterized using male-specific lethal-2 mRNA (msl-2) as a model substrate. Here Sxl interacts with multiple regulatory sequences in both the 5’ and 3’ untranslated regions of the RNA and employs two distinct and mutually reinforcing regulatory mechanisms that interfere with translation initiation. While regulation via the 3’ UTR of msl-2 mRNA critically relies on the recruitment of the co-repressor protein Upstream of N-Ras (UNR), regulation via the 5’ UTR involves an upstream open reading frame (uORF).

Building on these findings we now aim to address the following questions:

• How does Sxl control the activity of the msl-2 upstream open reading frame? What are the underlying molecular mechanisms?
• Does Sxl control translation of RNAs other than msl-2? And if so, what are the mechanisms employed?
• Are there other RNA-binding proteins that control translation by mechanisms analogous to Sxl?