@article {Aeschimanne201900335, author = {Florian Aeschimann and Anca Neagu and Magdalene Rausch and Helge Gro{\ss}hans}, title = {let-7 coordinates the transition to adulthood through a single primary and four secondary targets}, volume = {2}, number = {2}, elocation-id = {e201900335}, year = {2019}, doi = {10.26508/lsa.201900335}, publisher = {Life Science Alliance}, abstract = {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{\textendash}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.}, URL = {https://www.life-science-alliance.org/content/2/2/e201900335}, eprint = {https://www.life-science-alliance.org/content/2/2/e201900335.full.pdf}, journal = {Life Science Alliance} }