Indeed, the Drosophila FMR1 and orthologs of Rin are involved with translatioNAs frs and CycB. Similarly, G3BP forms a complex with human Caprin and each interact with myc and CycD mRNAs. Both examples suggest a redundant regulation of those targets. There is absolutely no direct proof for the latter possibility. Having said that, G3BP associates with and translationally regulates tau mRNA in neuronal cells. In Drosophila, FMR1 negatively regulates futsch mRNA, and also the futsch mutant phenotype is suppressed by overexpression of Tau, suggesting a redundant function of Tau and Futsch. Lig impacts on Rin and slightly on Capr but not on FMR1 levels. Even so, ontion as double mutants resulted inside a lig like phenotype, suggesting that the activity of FMR1 and Capr is altered in a lig mutant circumstance. Our AP MS experiments also revealed DART1 as a physical binding partner of Lig.
Arginine methyl transferases are in a position to methylate RGG motifs and thereby modulate additional resources the binding capability to mRNAs. Interestingly, FMR1 includes a conserved RGG domain that can be methylated in Drosophila and humans. In humans, protein methyl transferase 1, the ortholog of DART1, mediates the arginine methylation of FMR1 to alter its binding affinity to mRNAs. Additionally, G3BP1, the mouse ortholog of Rin, includes an RGG domain that is definitely methylated by PRMT1 after stimulation of the Wnt signaling pathway to modulate the binding to b Catenin mRNA. The RGG domain of Rin is weakly conserved and lacks the RGG motifs. It truly is thus unclear regardless of whether Rin might be methylated within the truncated arginine glycine wealthy region. Like FMR1 and G3BP, Caprin contains RGG domains, and it was identified as binding partner of PRMT8, that is closely connected to PRMT1 at the sequence level.
Additional experiments are needed to resolve no matter whether Lig is involved in a DART1 mediated methylation of FMR1 and Rin below specific situations, or no matter if Lig alters the activity of FMR1 and Capr by yet another mechanism. Lig, FMR1, Rin and Capr have been selelck kinase inhibitor identified as interactors of Orb in Co IP experiments, suggesting a complex formation of these proteins. Complex formation has been reported for G3BP and Caprin in human cell lines and for Capr and FMR1 in Drosophila and mouse neurons so far. We have been in a position to demonstrate that Rin, Capr and FMR1 have a redundant function within the eye, and that they localize in the similar subcellular structure in cultured Drosophila cells.
This raises the question whether or not the three RNA binding proteins Capr, Rin and FMR1 are functionally related only within the eye. Systematic analyses of the phenotypes of double mutant combinations will reveal the tissues in which these RNA binding proteins exert redundant and non redundant functions. In addition, it will be fascinating to determine no matter whether Rin and Capr contribute to phenotypes related to the FXS.