nhl-2 Modulates MicroRNA Activity in Caenorhabditis elegans

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2009.01.053 Byline: Christopher M. Hammell (1), Isabella Lubin (1), Peter R. Boag (2), T. Keith Blackwell (2), Victor Ambros (1) Keywords: RNA; DEVBIO; STEMCELL Abstract: 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. Author Affiliation: (1) Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA (2) Joslin Diabetes Center, Department of Pathology, Harvard Medical School, Harvard Stem Cell Institute, One Joslin Place, Boston, MA 02215, USA Article History: Received 28 August 2008; Revised 19 December 2008; Accepted 28 January 2009 Article Note: (miscellaneous) Published: March 5, 2009