The Caenorhabditis elegans pumilio homolog, puf-9, is required for the 3'UTR-mediated repression of the let-7 microRNA target gene, hbl-1

Dev Biol. 2007 May 15;305(2):551-63. doi: 10.1016/j.ydbio.2007.02.040. Epub 2007 Mar 3.

Abstract

The Puf family of RNA-binding proteins directs cell fates by regulating gene expression at the level of translation and RNA stability. Here, we report that the Caenorhabditis elegans pumilio homolog, puf-9, controls the differentiation of epidermal stem cells at the larval-to-adult transition. Genetic analysis reveals that loss-of-function mutations in puf-9 enhance the lethality and heterochronic phenotypes caused by mutations in the let-7 microRNA (miRNA), while suppressing the heterochronic phenotypes of lin-41, a let-7 target and homolog of Drosophila Brat. puf-9 interacts with another known temporal regulator hbl-1, the Caenorhabditis elegans ortholog of hunchback. We present evidence demonstrating that puf-9 is required for the 3'UTR-mediated regulation of hbl-1, in both the hypodermis and the ventral nerve cord. Finally, we show that this regulation is dependent on a region of the hbl-1 3'UTR that contains putative Puf family binding sites as well as binding sites for the let-7 miRNA family, suggesting that puf-9 and let-7 may mediate hypodermal seam cell differentiation by regulating common targets.

Publication types

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

MeSH terms

  • 3' Untranslated Regions / physiology*
  • Animals
  • Animals, Genetically Modified
  • Binding Sites / genetics
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans Proteins / biosynthesis
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Caenorhabditis elegans Proteins / physiology
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Down-Regulation / physiology*
  • Drosophila Proteins / physiology
  • Helminth Proteins / genetics
  • Helminth Proteins / metabolism
  • Helminth Proteins / physiology*
  • MicroRNAs / antagonists & inhibitors*
  • MicroRNAs / genetics*
  • MicroRNAs / physiology
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / physiology
  • Repressor Proteins / genetics*
  • Sequence Homology, Nucleic Acid
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • 3' Untranslated Regions
  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Helminth Proteins
  • MicroRNAs
  • Puf-9 protein, C elegans
  • RNA-Binding Proteins
  • Repressor Proteins
  • Transcription Factors
  • hbl-1protein, C elegans
  • let-7 microRNA, C elegans
  • pum protein, Drosophila