tudor-domain containing protein 5-primepromotes male sexual identity in theDrosophilagermline and is repressed in females bySex lethal

Abstract

For sexually reproducing organisms, production of male or female gametes depends on specifying the correct sexual identity in the germline. In D. melanogaster, Sex lethal (Sxl) is the key gene that controls sex determination in both the soma and the germline, but how it does so in the germline is unknown, other than that it is different than in the soma. We conducted an RNA expression profiling experiment to identify direct and indirect germline targets of Sxl specifically in the undifferentiated germline. We find that, in these cells, Sxl loss does not lead to a global masculinization observed at the whole-genome level. In contrast, Sxl appears to affect a discrete set of genes required in the male germline, such as Phf7. We also identify tudor domain containing protein 5-prime (tdrd5p) as a target for Sxl regulation that is important for male germline identity. tdrd5p is repressed by Sxl in female germ cells, but is highly expressed in male germ cells where it promotes proper male fertility and germline differentiation. Additionally, Tdrd5p localizes to cytoplasmic granules with some characteristics of RNA Processing (P-) Bodies, suggesting that it promotes male identity in the germline by regulating post-transcriptional gene expression.Author summaryLike humans, all sexually reproducing organisms require gametes to reproduce. Gametes are made by specialized cells called germ cells, which must have the correct sexual identity information to properly make sperm or eggs. In fruit flies, germ cell sexual identity is controlled by the RNA-binding protein Sxl, which is expressed only in females. To better understand how Sxl promotes female identity, we conducted an RNA expression profiling experiment to identify genes whose expression changes in response to the loss of Sxl from germ cells. Here, we identify tudor domain containing protein 5-prime (tdrd5p), which is expressed 17-fold higher in ovaries lacking Sxl compared to control ovaries. Additionally, tdrd5p plays an important role in males as male flies that are mutant for this gene cannot make sperm properly and thus are less fertile. Moreover, we find that tdrd5p promotes male identity in the germline, as several experiments show that it can shift the germ cell developmental program from female to male. This study tells us that Sxl promotes female identity in germ cells by repressing genes, like tdrd5p, that promote male identity. Future studies into the function of tdrd5p will provide mechanistic insight into how this gene promotes male identity.

The histone code reader PHD finger protein 7 controls sex-linked disparities in gene expression and malignancy in Drosophila

“…Ectopic Phf7-RC expression in mbt tumors and the overlap of the TSS of Phf7-RC with a L(3)mbt binding site identified in cephalic complex samples from third instar larvae ( 30 ) suggest that repression of Phf7-RC in the soma may depend on L(3)mbt itself. Something similar may apply to another M-pSDS protein, CG15930, also known as Tudor-domain–containing protein 5-prime (Tdrd5p), that is also normally highly expressed in male germ cells and is repressed by Sxl in female germ cells ( 34 , 37 ). Expression of CG15930 is strongly up-regulated in mbt tumors of both sexes and, like Phf7-RC , more so in males than in females.…”

“…Included among these is the CG15930 gene referred to above, which we have previously shown to be essential for mbt tumor growth ( 31 ). In wild-type flies, CG15930 localizes to cytoplasmic granules with some characteristics of RNA processing (P-) bodies and has been shown to promote proper male fertility and germline differentiation ( 37 ). Likewise, the overlap between genes controlled by Phf7 in testis and those dysregulated in mbt is negligible.…”