A new role for the GARP complex in microRNA-mediated gene regulation.
Many core components of the microRNA pathway have been elucidated and knowledge of their mechanisms of action actively progresses. In contrast, factors with modulatory roles on the pathway are just starting to become known and understood. Using a genetic screen in Caenorhabditis elegans, we identify a component of the GARP (Golgi Associated Retrograde Protein) complex, vps-52, as a novel genetic interactor of the microRNA pathway. The loss of vps-52 in distinct sensitized genetic backgrounds induces the enhancement of defective microRNA-mediated gene silencing. It synergizes with the core microRNA components, alg-1 Argonaute and ain-1 (GW182), in enhancing seam cell defects and exacerbates the gene silencing defects of the let-7 family and lsy-6 microRNAs in the regulation of seam cell, vulva and ASEL neuron development. Underpinning the observed genetic interactions, we found that VPS-52 impinges on the abundance of the GW182 proteins as well as the levels of microRNAs including the let-7 family. Altogether, we demonstrate that GARP complex fulfills a positive modulatory role on microRNA function and postulate that acting through GARP, vps-52 participates in a membrane-related process of the microRNA pathway.
Laval University Cancer Research Center, Hôtel-Dieu de Québec (Oncology-Centre Hospitalier Universitaire de Québec), Québec City, Québec, Canada.
Alejandro
A
Vasquez-Rifo
Gabriel D
GD
Bossé
Evelyne L
EL
Rondeau
Guillaume
G
Jannot
Alexandra
A
Dallaire
Martin J
MJ
Simard
D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000235:genetics*
C504319:AIN-1 protein, C elegans; C558782:ALG-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D033921:Vesicular Transport Proteins; C474488:let-7 microRNA, C elegans