The developmental timing regulator AIN-1 interacts with miRISCs and may target the argonaute protein ALG-1 to cytoplasmic P bodies in C. elegans

Mol Cell. 2005 Aug 19;19(4):437-47. doi: 10.1016/j.molcel.2005.07.013.

Abstract

In metazoans, microRNAs (miRNAs) carry out various regulatory functions through association with multiprotein miRNA-induced silencing complexes (miRISCs) that contain Dicer and Argonaute proteins. How miRNAs regulate the expression of their mRNA targets remains a major research question. We have identified the C. elegans ain-1 gene through a genetic suppressor screen and shown that it functions with the heterochronic genetic pathway that regulates developmental timing. Biochemical analysis indicates that AIN-1 interacts with protein complexes containing an Argonaute protein, Dicer, and miRNAs. AIN-1 shares homology with the candidate human neurological disease protein GW182, shown to localize in cytoplasmic processing bodies that are sites of mRNA degradation and storage. A functional AIN-1::GFP also localizes at the likely worm processing bodies. When coexpressed from transgenes, AIN-1 targets ALG-1 to the foci. These results suggest a model where AIN-1 regulates a subset of miRISCs by localization to the processing bodies, facilitating degradation or translational inhibition of mRNA targets.

MeSH terms

  • Animals
  • Caenorhabditis elegans / growth & development*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Differentiation
  • Cytoplasmic Structures / genetics
  • Cytoplasmic Structures / metabolism*
  • Endoribonucleases / genetics
  • Endoribonucleases / metabolism
  • Gene Expression Regulation, Developmental*
  • Gene Silencing
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Ribonuclease III

Substances

  • AIN-1 protein, C elegans
  • ALG-1 protein, C elegans
  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • MicroRNAs
  • RNA-Binding Proteins
  • Endoribonucleases
  • dcr-1 protein, C elegans
  • Ribonuclease III

Associated data

  • GENBANK/AAK32947