Sxl in translational repression of nanos mRNA
Sxl does not only regulate translation of msl-2 mRNA but controls protein synthesis from a complex group of Drosophila transcripts. This regulation mostly operates via 5’ UTR binding sites and involves uORFs that are present in the targeted mRNAs.
Elaborate genetic studies have implicated Sxl also in the control of translation of nanos mRNA in the female germline. But here Sxl-mediated translational repression involves a single binding site located in the 3’ UTR. Previous studies have convincingly demonstrated that SXL operating via such 3’ UTR binding sites cannot regulate translation by itself but relies on the recruitment of a co-repressor protein to the RNA. In contrast to msl-2 mRNA, we could not identify a UNR-binding site adjacent to the SXL binding motif in nanos mRNA, suggesting that nanos translational repression by Sxl differs from repression of msl-2 mRNA. But if regulation of nanos mRNA does not involve UNR, what other co-repressor does Sxl recruit then?
Nanos protein itself is a translational repressor which is involved in control of several differentiation genes. Failure to repress Nanos production in cystoblasts and early cysts of the female germline prevents cellular differentiation and results in formation of germline tumors. Hence, ablation of Sxl expression in the female germline results in tumorous overgrowth.
A similar phenotype has been described for a number of Drosophila genes and at least three additional ones have been shown to directly impact on nanos translation: Bam, Mei-P26 and Bgcn. Mutant alleles of these factors exhibit ectopic expression of Nanos protein in cystoblasts even in the presence of functional Sxl. Moreover, all four proteins are suggested to form a complex in the female germline. What remains entirely unclear is how complex formation is orchestrated, how it associates with the RNA (it contains three RNA-binding proteins) and how function is elicited – aspects of which we are studying in the lab.