Translational control in Drosophila

Research on conserved RBPs can be greatly advanced when using model organisms to understand their molecular mechanisms of action. We have previously used Drosophila to understand the functional versatility of UNR (in humans called CSDE1), an evolutionarily conserved protein for which we have found roles as an oncogene. UNR performs sex-specific functions in X-chromosome dosage compensation by binding to sex-specific targets and/or co-factors and regulating translation (in females) or lncRNA structure (in males). We are interested in understanding how UNR and its co-factor SXL regulate translation in Drosophila. The functional plasticity of UNR suggests that it could also function as a tumor suppressor depending on context, an issue we are currently testing using primary mouse keratinocytes.

Another conserved RBP is Dicer. We have shown that Drosophila Dicer-2, a protein normally involved in RNAi, has an additional role as a translation regulator. Dicer-2 promotes cytoplasmic poly(A) tail elongation, with the subsequent increase in translation of its targets.