let-7 coordinates the transition to adulthood through a single primary and four secondary targets

Life Sci Alliance. 2019 Mar 25;2(2):e201900335. doi: 10.26508/lsa.201900335. Print 2019 Apr.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Animals, Genetically Modified
  • CRISPR-Associated Protein 9 / genetics
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans Proteins / genetics*
  • DNA-Binding Proteins / genetics
  • Female
  • Gene Expression Regulation, Developmental / genetics*
  • Male
  • MicroRNAs / genetics*
  • Phenotype
  • Sexual Maturation / genetics*
  • Trans-Activators / genetics
  • Transcription Factors / genetics*
  • Transgenes
  • Vulva / growth & development


  • Caenorhabditis elegans Proteins
  • DMD-3 protein, C elegans
  • DNA-Binding Proteins
  • LIN-29 protein, C elegans
  • LIN-41 protein, C elegans
  • Mab-3 protein, C elegans
  • MicroRNAs
  • Trans-Activators
  • Transcription Factors
  • let-7 microRNA, C elegans
  • mab-10 protein, C elegans
  • CRISPR-Associated Protein 9