Certainly, the Drosophila FMR1 and orthologs of Rin are involved in translational regulation of growth regulatory genes in particular tissues. For instance, FMR1 binds bantam miRNA, an inhibitor of the pro apoptotic gene hid, and regulates cbl, which encodes a component on the EGFR signaling pathway, in germline stem cells. Nonetheless, bantam miRNA isn’t regulated by FMR1 in epithelial cells, and Lig was unable to regulate a bantam miRNA reporter. Furthermore, the expression of a pointed transcriptional reporter was unchanged in lig mutant clones, suggesting that cbl regulation by FMR1 is distinct to the germline or has only subtle effects inside the establishing eye. The Rin ortholog G3BP controls myc, CyclinD2, cdk7 and cdk9 mRNA. Nevertheless, it is actually not known irrespective of whether this function is conserved for Rin, and we did not observe any alterations of Myc protein levels in lig mutant clones.
It will likely be crucial to identify mRNAs that are regulated by FMR1, Capr and Rin in epithelial tissues in the course of development, and to identify whether or not Lig mediates specificity for specific mRNAs. To recognize the signaling pathway that is definitely regulated by Lig, we put to use readouts for the Hippo, EGFR, Insulin, Hedgehog, Wnt and JAK/STAT signaling pathways. a fantastic read We observed no alterations of all analyzed pathways except for the highly conserved JAK/STAT signaling pathway. The pathway is composed of four modules: the ligands, Upd, Upd2 and Upd3, the receptor Domeless, the receptor linked Janus kinase Hopscotch, along with the signal transducer and activator of transcription STAT92E. The involvement of Lig inside the JAK/STAT signaling pathway leads to a number of assumptions and queries inside the context of our findings.
Initial, the autonomous impact of Lig on the 10xSTAT92E GFP reporter suggests that Lig regulates the intracellular elements or modifiers thereof as an alternative to expression in the ligands, which would lead to non autonomous effects. Second, the physical and genetic the original source interactions of Lig with all the mRNA binding proteins FMR1, Capr and Rin raises the question no matter whether Lig directly impacts on the JAK/STAT pathway or whether or not it modulates the JAK/STAT signaling by means of FMR1, Capr and Rin. So far, we cannot exclude either option. Even so, it was lately demonstrated that upd and STAT92E mRNAs are targets for posttranscriptional regulation through the miRNA pathway. It will be exciting to figure out whether FMR1, Rin or Capr are involved within this procedure within the case of STAT92E.
Our information supply evidence that FMR1, Capr and Rin function within a redundant manner in epithelial tissues in development control, suggesting that they regulate either overlapping sets of mRNAs or unique mRNAs encoding proteins with redundant functions. Examples for the former have been described for FMR1, Capr and G3BP, the human ortholog of Rin.