The temporal patterning microRNA let-7 regulates several transcription factors at the larval to adult transition in C. elegans

Dev Cell. 2005 Mar;8(3):321-30. doi: 10.1016/j.devcel.2004.12.019.

Abstract

The let-7 microRNA is phylogenetically conserved and temporally expressed in many animals. C. elegans let-7 controls terminal differentiation in a stem cell-like lineage in the hypodermis, while human let-7 has been implicated in lung cancer. To elucidate let-7's role in temporal control of nematode development, we used sequence analysis and reverse genetics to identify candidate let-7 target genes. We show that the nuclear hormone receptor daf-12 is a let-7 target in seam cells, while the forkhead transcription factor pha-4 is a target in the intestine. Additional likely targets are the zinc finger protein die-1 and the putative chromatin remodeling factor lss-4. Together with the previous identification of the hunchback ortholog hbl-1 as a let-7 target in the ventral nerve cord, our findings show that let-7 acts in at least three tissues to regulate different transcription factors, raising the possibility of let-7 as a master temporal regulator.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Body Patterning / physiology*
  • Caenorhabditis elegans / growth & development*
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / metabolism*
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Developmental / physiology
  • Intestinal Mucosa / metabolism
  • Intestines / growth & development
  • Larva / growth & development
  • Larva / metabolism
  • MicroRNAs / metabolism*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Trans-Activators / metabolism
  • Transcription Factors / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • DAF-12 protein, C elegans
  • DIE-1 protein, C elegans
  • DNA-Binding Proteins
  • MicroRNAs
  • Pha-4 protein, C elegans
  • Receptors, Cytoplasmic and Nuclear
  • Trans-Activators
  • Transcription Factors
  • hbl-1protein, C elegans
  • let-7 microRNA, C elegans