Mechanisms ensuring robust repression of the Drosophila female germline stem cell maintenance factor Nanos via posttranscriptional regulation

During oogenesis in theDrosophilaovary, numerous translational regulators promote the self-renewal or differentiation of stem cells. An intriguing question is how these regulators combine to execute translational regulation. Here, we study mechanisms for the posttranscriptional regulation ofnos, a critical stem cell self-renewal factor in theDrosophilaovary; specifically, regulators that promote differentiation of the stem cell daughter. Previous studies showed that Bam, Bgcn, Mei-P26, and Sxl form a complex and repressnosexpression through thenos3 ' UTR. To further elucidate mechanistic processes of Nos translational regulation, we reconstitutednosrepression in culturedDrosophilacells. We identify Ago1 and Brat as new members, and show that Ago1 acts through miRNA binding sites in the proximal region of thenos3 ' UTR, whereas Sxl acts via an Sxl binding sequence in the distal region. Combining these findings with published reports, we propose that additional factors Bam, Bgcn, Mei-P26, and Brat are recruited tonosmRNAs through interaction with Ago1 and Sxl. These findings elucidate mechanisms ofnosregulation by diverse translational repressors.