Growth suppressor lingerer regulates bantam microRNA to restrict organ size

The evolutionarily conserved Hippo signaling pathway plays an important role in organ size control by regulating cell proliferation and apoptosis. Here, we identify Lingerer (Lig) as a growth suppressor using RNAi modifying screen in Drosophila melanogaster. Loss of lig increases organ size and upregulates bantam (ban) and the expression of the Hippo pathway target genes, while overexpression of lig results in diminished ban expression and organ size reduction. We demonstrate that Lig C-terminal exhibits dominant-negative function on growth and ban expression, and thus plays an important role in organ size control and ban regulation. In addition, we provide evidence that both Yki and Mad are essential for Lig-induced ban expression. We also show that Lig regulates the expression of the Hippo pathway target genes partially via Yorkie. Moreover, we find that Lig physically interacts with and requires Salvador to restrict cell growth. Taken together, we demonstrate that Lig functions as a critical growth suppressor to control organ size via ban and Hippo signaling.