In-depth study of lin-28 suggests selectively conserved let-7 independent mechanism in Drosophila

Abstract

Lin-28 is a conserved RNA-binding protein that is involved in a wide range of developmental processes and pathogenesis. At the molecular level, Lin-28 blocks the maturation of let-7 and regulates translation of certain mRNA targets. In Drosophila, Lin-28 is reported to play a role in oogenesis, muscle formation, and the symmetric division of adult intestinal stem cells. In this study, we characterized Drosophila Lin-28 through a detailed examination of its temporal and spatial expression. Lin-28 is specifically expressed in embryonic nervous and cardiac systems. However, loss or gain of lin-28 function does not cause any abnormality during embryonic development. Instead, the ubiquitous overexpression of Lin-28 leads to lethality from late larval stage to pupal stage, and eye-specific overexpression causes severe cell loss. The ectopic expression of human Lin28A has the same effect as Drosophila Lin-28, indicating functional conservation in Lin-28 orthologs. We also examined the effect of Lin-28 on let-7 biogenesis through the mutant and overexpression analysis. Lin-28 does not block the production of let-7 in Drosophila, which suggests the let-7 independent pathway as a molecular mechanism of Lin-28.