TY - JOUR T1 - <em>let-7</em> coordinates the transition to adulthood through a single primary and four secondary targets JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.201900335 VL - 2 IS - 2 SP - e201900335 AU - Florian Aeschimann AU - Anca Neagu AU - Magdalene Rausch AU - Helge Großhans Y1 - 2019/04/01 UR - https://www.life-science-alliance.org/content/2/2/e201900335.abstract N2 - The juvenile-to-adult (J/A) transition, or puberty, is a period of extensive changes of animal body morphology and function. The onset of puberty is genetically controlled, and the let-7 miRNA temporally regulates J/A transition events in nematodes and mammals. Here, we uncover the targets and downstream pathways through which Caenorhabditis elegans let-7 controls male and female sexual organ morphogenesis and skin progenitor cell fates. We find that let-7 directs all three processes by silencing a single target, the post-transcriptional regulator lin-41. In turn, the RNA-binding protein LIN41/TRIM71 regulates these processes by silencing only four target mRNAs. Thus, by silencing LIN41, let-7 activates LIN-29a and MAB-10 (an early growth response-type transcription factor and its NAB1/2-orthologous cofactor, respectively) to terminate progenitor cell self-renewal and to promote vulval integrity. By contrast, let-7 promotes development of the male sexual organ by up-regulating DMD-3 and MAB-3, two Doublesex/MAB-3 domain–containing transcription factors. Our results provide mechanistic insight into how a linear chain of post-transcriptional regulators diverges in the control of a small set of transcriptional regulators to achieve a coordinated J/A transition. ER -