nhl-2 Modulates microRNA activity in Caenorhabditis elegans

Cell. 2009 Mar 6;136(5):926-38. doi: 10.1016/j.cell.2009.01.053.


TRIM-NHL proteins represent a large class of metazoan proteins implicated in development and disease. We demonstrate that a C. elegans TRIM-NHL protein, NHL-2, functions as a cofactor for the microRNA-induced silencing complex (miRISC) and thereby enhances the posttranscriptional repression of several genetically verified microRNA targets, including hbl-1 and let-60/Ras (by the let-7 family of microRNAs) and cog-1 (by the lsy-6 microRNA). NHL-2 is localized to cytoplasmic P-bodies and physically associates with the P-body protein CGH-1 and the core miRISC components ALG-1/2 and AIN-1. nhl-2 and cgh-1 mutations compromise the repression of microRNA targets in vivo but do not affect microRNA biogenesis, indicating a role for an NHL-2:CGH-1 complex in the effector phase of miRISC activity. We propose that the NHL-2:CGH-1 complex functions in association with mature miRISC to modulate the efficacy of microRNA:target interactions in response to physiological and developmental signals, thereby ensuring the robustness of genetic regulatory pathways regulated by microRNAs.

Publication types

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

MeSH terms

  • Animals
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cytoplasmic Granules / metabolism
  • Homeodomain Proteins / metabolism
  • MicroRNAs / metabolism*
  • RNA Nucleotidyltransferases / genetics
  • RNA Nucleotidyltransferases / metabolism
  • RNA, Helminth / metabolism*
  • RNA-Induced Silencing Complex / metabolism


  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Homeodomain Proteins
  • MicroRNAs
  • NHL-2 protein, C elegans
  • RNA, Helminth
  • RNA-Induced Silencing Complex
  • cog-1 protein, C elegans
  • RNA Nucleotidyltransferases
  • cgh-1 protein, C elegans