Lin28 Represses Hub Cell microRNAs to Maintain Drosophila Testis Niche Function

In the Drosophila testis, hub cells form a specialized niche that sustains adjacent stem cells. The RNA-binding protein Lin28 is expressed in hub cells and is essential for their maintenance and niche function; however, the underlying mechanisms remain poorly understood. Lin28 is well-characterized as a suppressor of let-7 biogenesis, raising the possibility that Lin28 regulates let-7 and additional microRNAs to preserve hub cell identity. We performed genome-wide microRNA expression profiling and identified a set of microRNAs upregulated in lin28 mutant testes, including let-7, demonstrating that Lin28 represses let-7 in hub cells to protect let-7-targeted hub cell factors. Here, we report genetic analysis of miR-304, a microRNA identified from the profiling. miR-304 contains a seed site complementary to the 3' UTR of the IGF-II mRNA-binding protein (IMP), a critical hub-specific factor. We find that miR-304 mutant testes exhibit elevated levels of IMP specifically in hub cells, suggesting that miR-304 targets imp mRNAs and reduces imp expression in hub cells. Thus, in wild-type hub cells, Lin28 represses miR-304 to maintain IMP expression. We propose that Lin28 preserves niche function by restraining multiple microRNAs, thereby protecting essential hub cell factors from microRNA-mediated silencing.