Transcription of the C. elegans let-7 microRNA is temporally regulated by one of its targets, hbl-1

Dev Biol. 2009 Oct 15;334(2):523-34. doi: 10.1016/j.ydbio.2009.07.012. Epub 2009 Jul 21.

Abstract

The let-7 family of microRNAs (miRNAs) are important regulators of developmental timing and cell differentiation and are often misexpressed in human cancer. In C. elegans, let-7 controls cell fate transitions from larval stage 4 (L4) to adulthood by post-transcriptionally down-regulating lineage-abnormal 41 (lin-41) and hunchback-like 1 (hbl-1). Primary let-7 (pri-let-7) transcripts are up-regulated in the L3, yet little is known about what controls this transcriptional up-regulation. We sought factors that either turn on let-7 transcription or keep it repressed until the correct time. Here we report that one of let-7's targets, the transcription factor Hunchback-like 1 (HBL-1), is responsible for inhibiting the transcription of let-7 in specific tissues until the L3. hbl-1 is a known developmental timing regulator and inhibits adult development in larval stages. Therefore, one important function of HBL-1 in maintaining larval stage fates is inhibition of let-7. Indeed, our results reveal let-7 as the first known target of the HBL-1 transcription factor in C. elegans and suggest a negative feedback loop mechanism for let-7 and HBL-1 regulation.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / physiology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Feedback, Physiological
  • Gene Expression Regulation, Developmental
  • Genes, Reporter
  • Larva
  • MicroRNAs / genetics
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • RNA Interference
  • RNA, Small Interfering / pharmacology
  • Sequence Alignment
  • Sequence Homology, Nucleic Acid
  • Time Factors
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Transcription, Genetic*

Substances

  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • MicroRNAs
  • RNA, Small Interfering
  • Transcription Factors
  • hbl-1protein, C elegans
  • lin-4 microRNA, C elegans