A genetic interactome of the let-7 microRNA in C. elegans

Dev Biol. 2015 May 15;401(2):276-86. doi: 10.1016/j.ydbio.2015.02.013. Epub 2015 Feb 27.


The heterochronic pathway controls temporal patterning during Caenorhabditis elegans larval development. The highly conserved let-7 microRNA (miRNA) plays a key role in this pathway, directing the larval-to-adult (L/A) transition. Hence, knowledge of the genetic interactome of let-7 has the potential to provide insight into both control of temporal cell fates and mechanisms of regulation and function of miRNAs. Here, we report the results of a genome-wide, RNAi-based screen for suppressors of let-7 mutant vulval bursting. The 201 genetic interaction partners of let-7 thus identified include genes that promote target silencing activity of let-7, seam cell differentiation, or both. We illustrate the suitability of our approach by uncovering the mitotic cyclin-dependent kinase CDK-1 as a downstream effector of let-7 that affects both seam cell proliferation and differentiation, and by identifying a core set of candidate modulators of let-7 activity, which includes all subunits of the condensin II complex. We propose that the genes identified in our screen thus constitute a valuable resource for studies of the heterochronic pathway and miRNAs.

Keywords: C. elegans; CDC-25.2; CDK-1; Cell cycle; Condensin; Condensin II complex; Developmental timing; Differentiation; Heterochronic; Hypodermis; LIN-29; NCC-1; Vulva; col-19; let-7; miRNA regulation; miRNA target; microRNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Animals
  • Body Patterning / genetics*
  • CDC2 Protein Kinase / biosynthesis
  • CDC2 Protein Kinase / genetics*
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans Proteins / genetics
  • Cell Differentiation / genetics
  • DNA-Binding Proteins / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • MicroRNAs / genetics*
  • Multiprotein Complexes / genetics
  • RNA Interference
  • Transcription Factors / genetics


  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • LIN-29 protein, C elegans
  • MicroRNAs
  • Multiprotein Complexes
  • Transcription Factors
  • condensin complexes
  • let-7 microRNA, C elegans
  • CDC2 Protein Kinase
  • Adenosine Triphosphatases