Novel roles for RNA binding proteins squid, hephaesteus, and Hrb27C in Drosophila oogenesis

Reproductive capacity in many organisms is maintained by germline stem cells (GSCs). A complex regulatory network influences stem cell fate, including intrinsic factors, local signals, and hormonal and nutritional cues. Posttranscriptional regulatory mechanisms ensure proper cell fate transitions, promoting germ cell differentiation to oocytes. As essential RNA binding proteins with constitutive functions in RNA metabolism, heterogeneous nuclear ribonucleoproteins (hnRNPs) have been implicated in GSC function and axis specification during oocyte development. HnRNPs support biogenesis, localization, maturation, and translation of nascent transcripts. Whether and individual hnRNPs specifically regulate GSC function has yet to be explored.

We demonstrate that hnRNPs are expressed in distinct patterns in the Drosophila germarium. We show that three hnRNPs, squid, hephaestus, and Hrb27C are cell-autonomously required in GSCs for their maintenance. Although these hnRNPs do not impact adhesion of GSCs to adjacent cap cells, squid and hephaestus (but not Hrb27C) are necessary for proper bone morphogenetic protein signaling in GSCs. Moreover, Hrb27C promotes proper GSC proliferation, whereas hephaestus promotes cyst division.

We find that hnRNPs are independently and intrinsically required in GSCs for their maintenance in adults. Our results support the model that hnRNPs play unique roles in stem cells essential for their self-renewal and proliferation.