nhl-2 Modulates microRNA activity in Caenorhabditis elegans.
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.
Hammell
Christopher M
CM
University of Massachusetts Medical School, Worcester, 01605, USA.
Lubin
Isabella
I
Boag
Peter R
PR
Blackwell
T Keith
TK
Ambros
Victor
V
D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism*; D012316:RNA Nucleotidyltransferases / Q000235:genetics / Q000378:metabolism; D018510:RNA, Helminth / Q000378:metabolism*; D034743:RNA-Induced Silencing Complex / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D018398:Homeodomain Proteins; D035683:MicroRNAs; C539315:NHL-2 protein, C elegans; D018510:RNA, Helminth; D034743:RNA-Induced Silencing Complex; C491329:cog-1 protein, C elegans; D012316:RNA Nucleotidyltransferases; C490618:cgh-1 protein, C elegans